GEO 数据集

主题由标题与摘要自动归类；样本量为数据集标注之和，SuperSeries 可能与其 SubSeries 重复计算。

• KLF16 and SIN3A facilitate endometrial cancer cell proliferation in association with CTD-2377D24.6
  GSE349296Homo sapiens6 个样本2026-10-31

  Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Pathogenetically, most cases arise from uncontrolled proliferative expansion of endometrial cells under prolonged estrogen stimulation, ultimately leading to malignant transformation within the glandular epithelium. Identifying key regulators of aberrant endometrial proliferation is therefore critical for developing novel therapeutic modalities against EC. In the present study, we characterized Kruppel-like factor 16 (KLF16), a transcription factor that drives proliferative signaling across multiple cellular components of the endometrium, including endothelial, epithelial, and smooth muscle cell types. Clinicopathological analysis revealed significantly elevated KLF16 expression in human EC tissues, which was positively associated with both advanced tumor stages and high histological grades. Genetic perturbation experiments demonstrated that knockdown of KLF16 robustly inhibited endometrial cancer cell proliferation in vitro and impeded tumor growth in vivo. Given its role as a master regulator controlling broad transcriptomic programs encompassing both protein-coding genes and non-coding RNAs, we performed unbiased screening and identified lncRNA CTD-2377D24.6 as a potential downstream mediator associated with KLF16 signaling. Notably, overexpression of CTD-2377D24.6 effectively counteracted the anti-proliferative effects induced by KLF16 depletion. Mechanistically, single-cell transcriptomics, coimmunoprecipitation, and functional assays demonstrated that SIN3A interacts with KLF16 and may contribute to the association between KLF16 and CTD-2377D24.6 expression, which is linked to enhanced endometrial cancer cell proliferation. Together, these findings established KLF16 contributes to endometrial cancer progression and highlight the KLF16/SIN3A/CTD-2377D24.6-associated regulatory axis as a potential molecular pathway relevant to EC proliferation.

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• Targeting EGR1 Attenuates CCL2 Expression in Inflammatory Keratinocytes and Allergic Skin Inflammation
  GSE349203Homo sapiens5 个样本2026-10-31

  Early growth response 1 (EGR1) is a zinc-finger transcription factor involved in inflammatory gene regulation, but the extent to which pharmacological inhibition of EGR1 DNA-binding activity influences inflammatory transcriptional responses in keratinocytes remains incompletely understood. Here, we explored the transcriptional effects of pharmacological EGR1 inhibition in tumor necrosis factor-α (TNFα)-stimulated HaCaT keratinocytes. RNA sequencing was employed as an exploratory, hypothesis-generating screen using three structurally related EGR1 inhibitors (IT21, IT23, and IT25) to identify candidate genes showing concordant expression patterns across the three pharmacological perturbations. This analysis suggested broader changes in inflammation-associated transcriptional programs and identified several leukocyte-recruiting chemokines among the candidate genes. CCL2 was selected as a representative candidate for independent biological and mechanistic validation. IT25 treatment and EGR1 knockdown attenuated TNFα-induced CCL2 expression, while promoter-reporter analysis, EGR1-binding site mutagenesis, EGR1 overexpression, and chromatin immunoprecipitation supported EGR1-dependent transcriptional regulation of CCL2 in keratinocytes. Furthermore, topical IT25 treatment attenuated house dust mite-induced atopic dermatitis-like skin inflammation and was associated with reduced epidermal CCL2 expression and inflammatory cell infiltration in vivo. Collectively, these findings establish EGR1-dependent regulation of CCL2 in inflammatory keratinocytes and support further investigation of EGR1 DNA-binding activity as a pharmacological target in cutaneous inflammation.

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• Exposure to perfluorooctanoic acid perturbs serotonin signaling in maternal pancreatic islets and induces gestational diabetes in mice
  GSE330582Mus musculus8 个样本2026-10-31

  [working abstract for manuscript, in style of how is required for EHP] Background: Perfluorooctanoic acid (PFOA) has been linked to gestational diabetes and other adverse pregnancy outcomes in humans. Despite the association, the mechanisms by which PFOA contributes to GDM have not been studied. The present study investigated whether PFOA exposure resulted in lower pancreatic islet serotonin abundance and β-cell proliferation, glucose intolerance, impaired insulin secretion, insulin resistance, and robust transcriptional changes underlying pancreatic islet adaptation, which provided evidence for a mechanism of PFOA-induced GDM. Objectives: The purpose of this study was to assess whether PFOA exposure impairs pancreatic islet serotonin-driven β-cell proliferation and causes GDM in a C57BL/6J mouse model. Methods: Analysis of pancreatic islet serotonin abundance and β-cell proliferation were measured by immunofluorescence. Metabolic assays, including glucose tolerance test, glucose-stimulated insulin secretion, and insulin tolerance test were used to characterize GDM phenotypes. Bulk RNA sequencing was used to analyze differentially expressed genes and gene set enrichment in pancreatic islets isolated from control and PFOA-exposed mice. Results: PFOA exposure lowered islet serotonin abundance and β-cell proliferation in gestational day (GD) 12.5 pregnant dams. PFOA exposure was associated with glucose intolerance, impaired insulin secretion, and insulin resistance in GD16.5 pregnant dams. β-cell proliferation at GD12.5 and glucose tolerance at GD16.5 was improved in PFOA-exposed dams treated with a serotonin receptor 2B agonist (BW-732C86). RNAseq uncovered four differentially expressed genes and a broad reduction in coordinated transcriptional pathway activity in maternal pancreatic islets of PFOA-exposed GD12.5 dams. Discussion: PFOA-induced glucose intolerance was associated with perturbed pancreatic islet serotonin abundance.

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• Comparative profiling of SARS-CoV-2 variant infections reveals diverse impacts on host cell RNA and RNA binding protein distribution and regulation
  GSE318110Homo sapiens14 个样本2026-10-31

  RNA viruses perturb cellular RNA metabolism to promote viral transcript expression and genome replication. However, the extent of host cell RNA reprogramming and the consequences on RNA binding protein (RBP) expression and localization remain poorly understood. Here, we utilized an integrated set of transcriptomics, proteomics, and high-content imaging approaches to compare the impact of different SARS-CoV-2 variants, including an early viral isolate and later emerging variants of concern (Alpha, Delta and Omicron) on the host cellular RNA and RBP landscapes. While all variants deeply remodelled the host transcriptome in a subcellular compartment-specific manner, we found that Omicron variants express lower levels of viral RNA products compared to earlier variants, while still driving efficient production of viral proteins. The surge in viral RNA expression correlated with altered subcellular RNA biotype distribution, cytoplasmic mRNA exclusion, the selective disruption of the localization of polyA-tail interacting proteins, and the nuclear accumulation of non-coding transcripts such as RN7SL family members and MALAT-1. Unexpectedly, we found many RBPs that exhibiting altered subcellular localization following abiotic innate immune stimulation with poly(I:C) but remained unaltered in cells infected with SARS-CoV-2 variants, revealing a capacity for these viruses to limit the overall impact on the RBP subcellular distribution. Our results further indicate that Omicron infection sustains higher expression levels of proteins components of the signal recognition particle and translation factors, which may enable a more effective production of immune response and viral components. Altogether, this work highlights the deep impact of SARS-CoV-2 infection on host cell RNA regulatory landscape and provides new insights to explain the differential impact of Omicron compared to early SARS-CoV-2 variants.

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• CRISPR screen after venetoclax and azacitidine treatment in AML cells
  GSE314297Homo sapiens12 个样本2026-10-31

  CRISPR screen was performed in three isogenic MOLM-13 acute myeloid leukemia (AML) cell lines (p53 WT/p53 R248Q/p53 KO) to analyze gene dependencies changes after treatment with venetoclax and azacitidine.

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• Ribosome profiling of OTUD6B knockdown and scramble-control MDA-MB-231 cells
  GSE352635Homo sapiens4 个样本2026-10-30

  Ribosome profiling was performed in human MDA-MB-231 cells with shOTUD6B-41 or a scramble-control shRNA. Two independent biological replicates were included per group, yielding four paired-end sequencing libraries. Gene-level read counts and FPKM expression values were generated. This experiment and the Flag-OTUD6B eCLIP-seq experiment in HEK293T cells belong to the same research study.

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• RNA-seq and CRISPR screen after venetoclax and azacitidine treatment in AML cells
  GSE314299Homo sapiens30 个样本2026-10-30

  This SuperSeries is composed of the SubSeries listed below.

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• HOXA9 Couples Transcriptional Control with Higher-Order Chromatin Architecture in Acute Myeloid Leukemia [HiC]
  GSE306376Homo sapiens6 个样本2026-10-30

  The three-dimensional (3D) genome is organized by architectural proteins such as CTCF and cohesin, while transcription factors (TFs) typically regulate enhancer–promoter (E–P) and enhancer-enhancer (E-E) communications without major structural effects. How these layers intersect remains unclear. Here, we reveal that the homeobox TF HOXA9—overexpressed in ~50% of acute myeloid leukemia (AML)—exerts a non-canonical architectural role. HOXA9 depletion in AML cells disrupts topologically associating domain (TAD) boundaries, dissolves chromatin loops, and perturbs cell-specific gene programs. We identify a distinct class of long-range “hybrid” loops (>250 kb) co-anchored by HOXA9 and convergent CTCF, frequently linked to TAD boundaries. Integrative analysis defines a 3D genome informed HOXA9 network and identifies NHLRC2 as a direct downstream target essential for leukemogenesis. Our findings establish HOXA9 as a dual-function TF that couples transcriptional control with higher-order genome architecture, offering a new mechanism for its pervasive activation across molecularly diverse AML subtypes.

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• HOXA9 Couples Transcriptional Control with Higher-Order Chromatin Architecture in Acute Myeloid Leukemia [RNA-seq]
  GSE301086Homo sapiens8 个样本2026-10-30

  The three-dimensional (3D) genome is organized by architectural proteins such as CTCF and cohesin, while transcription factors (TFs) typically regulate enhancer–promoter (E–P) and enhancer-enhancer (E-E) communications without major structural effects. How these layers intersect remains unclear. Here, we reveal that the homeobox TF HOXA9—overexpressed in ~50% of acute myeloid leukemia (AML)—exerts a non-canonical architectural role. HOXA9 depletion in AML cells disrupts topologically associating domain (TAD) boundaries, dissolves chromatin loops, and perturbs cell-specific gene programs. We identify a distinct class of long-range “hybrid” loops (>250 kb) co-anchored by HOXA9 and convergent CTCF, frequently linked to TAD boundaries. Integrative analysis defines a 3D genome informed HOXA9 network and identifies NHLRC2 as a direct downstream target essential for leukemogenesis. Our findings establish HOXA9 as a dual-function TF that couples transcriptional control with higher-order genome architecture, offering a new mechanism for its pervasive activation across molecularly diverse AML subtypes.

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• HOXA9 reprograms 3D genome architecture to regulate oncogenic transcription in acute myeloid leukemia [CUT&RUN]
  GSE301083Homo sapiens31 个样本2026-10-30

  The hierarchical three-dimensional (3D) organization of chromatin underpins the spatial and temporal control of gene expression during development. This principle is exemplified by the Hox gene clusters, where dynamic topological architecture governs precise transcriptional activation. While disruption of chromatin organization at Hox genes is increasingly recognized in various human malignancies, the extent to which Hox genes themselves contribute to shaping 3D genome architecture remains poorly understood. In particular, it is unknown whether oncogenic overexpression of HOXA9—a highly conserved transcription factor and common downstream effector of diverse genetic alterations in acute myeloid leukemia (AML)—can actively reprogram chromatin topology. Here, we uncover a pivotal role for HOXA9 as a master regulator of 3D chromatin architecture in human AML. We demonstrate that HOXA9 orchestrates a leukemia-specific reconfiguration of chromatin topology. HOXA9 promotes the formation of leukemia specific topologically associating domains (TADs) and establishes long-range enhancer–promoter interactions essential for maintaining the leukemic transcriptional program. Perturbation of HOXA9 leads to widespread architectural collapse, marked by the dissolution of chromatin loops, disrupted enhancer communication, and silencing of critical leukemogenic genes. Furthermore, HOXA9-mediated chromatin looping occurs independently of CTCF. Instead, HOXA9 functions through the cohesin complex to facilitate higher-order genome organization, thereby functioning as a non-canonical architectural factor. Among its targets, we identify NHLRC2 as a HOXA9-associated loop gene essential for leukemic cell survival and proliferation. Collectively, these findings uncover a previously unappreciated architectural function of HOXA9 in modulating 3D genome organization and sustaining oncogenic gene expression in AML. More broadly, they suggest a mechanistic paradigm in which HOX transcription factors actively reprogram nuclear architecture to enforce lineage-specific or malignant gene expression programs.

  空间转录组扰动筛选
• Trisomy 21 Perturbs Oligodendrocyte Developmental States and Oligo-Neuron Communication in Human Forebrain Assembloids
  GSE352389Homo sapiens12 个样本2026-10-29

  Intellectual disability is a hallmark of Down syndrome (DS), caused by the triplication of human chromosome 21. Abnormal neuronal connectivity and impaired myelination are consistently observed in DS, yet the underlying mechanisms remain poorly understood. Here, we used DS-derived isogenic induced pluripotent stem cell-derived forebrain assembloids (FAs) to investigate oligodendrocyte lineage cell (OLLC) development and neuron-glia interactions. Trisomic FAs exhibited an expansion of BCAS1+ pre-myelinating OLLCs, without a corresponding increase in myelin basic protein (MBP) expression. Transcriptomic analyses identified a euploid-enriched, trophic and maturation-supportive state (OLLC_2-TMS) and a trisomy-enriched state, characterized by enhanced neuronal interactions and restricted progression beyond the pre-myelinating stage (OLLC_3-NID). These transcriptional signatures were also present in OLLCs from early postnatal human cortex. Increased excitatory neuronal contacts with pre-myelinating OLLCs accompanied ultrastructural myelin abnormalities in trisomic assembloids. Our findings suggest that trisomy redirects OLLC development toward a pre-myelinating state, uncoupling oligodendrocyte differentiation from productive myelination.

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• Prenatal maternal cold stress exposure drives sex-specific neurodevelopmental disruptions in the fetal hypothalamus
  GSE328919Mus musculus3 个样本2026-10-29

  The prevalence of neurodevelopmental disorders (NDDs) is increasing, with growing evidence implicating the intrauterine environment as a critical regulator of fetal brain development. Gestational perturbations such as maternal stress can increase NDD risk; however, the mechanism(s) by which prenatal maternal stress reshape fetal neurodevelopment remain unclear. Accordingly, the objective of my project was to characterize how maternal cold stress exposure during pregnancy disrupts neural stem and progenitor cell (NSPC) developmental programs in the fetus and the impact this has on neurodevelopment in the hypothalamus. Pregnant mice were exposed to 4°C for 30 minutes daily from embryonic day 11.5 (E11.5) to E15.5—a critical period of neurodevelopment in the hypothalamus. To assess how maternal cold stress impacts neural stem cell (NSC) behaviours, we employed the neurosphere assay, quantifying the number and size of primary and secondary neurospheres as a measure of NSC proliferation and self-renewal, respectively. Our findings revealed no change in NSC proliferation or self-renewal when comparing control and maternal cold stress male and female neurospheres. However, differentiation of dissociated NSCs revealed that neurons from both sexes had longer axons following maternal cold stress exposure. Interestingly, only male-derived cultures exhibited a significant increase in the number TUJ1+ neurons in response to maternal cold stress exposure, whereas only female-derived maternal cold stress cultures showed enhanced dendritic arborization. To explore the molecular basis of these changes, we performed single-cell RNA sequencing on E15.5 fetal hypothalamic NSPCs. Analysis of differentially expressed genes uncovered basal sex differences between the transcriptional signatures of control male and female Cycling NSPCs and suggested that maternal cold stress shifts female Cycling NSPCs toward a more male-like transcriptional profile. Gene ontology analysis revealed that maternal cold stress upregulates pathways linked to neuronal growth, development, and GABAergic neuron differentiation, but only in females. Importantly, ligand-receptor analysis suggested that maternal cold stress exposure disrupts neurodevelopmental programs through altered cell-cell signalling within Cycling NSPCs predominantly in females. These findings demonstrate that prenatal maternal cold stress exposure drives sex-specific effects on fetal neurodevelopment and uncover distinct cellular pathways that may contribute to sex differences seen in the presentation and risk of many NDDs.

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• Intestinal SAA1 and SAA2 regulate the balance between host inflammatory responses and metabolism
  GSE286869Mus musculus40 个样本2026-10-29

  Since their discovery as acute phase reactants, the SAA proteins have been an important focus of innate immunity research. Most SAA production is in the liver, and despite recent findings of their roles in promoting intestinal immunity, the precise functions of intestinal SAAs have not been well-studied. Validating and using an SAA1/2 double knock-out mouse, we found protective effects of SAA1 and SAA2 mitigating systemic and local inflammatory challenges, along with gene-, sex-, and location-specific responses to gut microbiota perturbations. SAA1 and SAA2 expression supports immunological protection in homeostasis but prioritizes metabolic activities under stress. From this work, we propose a new model in which SAA functions to regulate and integrate the interface between metabolism and host responses to inflammatory insults.

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• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [ASO]
  GSE328887Homo sapiens40 个样本2026-10-28

  Pseudouridines are abundant mRNA modifications that can impact splicing, translation, and stability to tune gene expression. PUS7 is one of the major mRNA pseudouridine synthases whose dysregulation leads to neurodevelopmental disorders and cancer, underscoring the critical function of PUS7-dependent pseudouridines. Beyond a short and degenerate consensus sequence, the molecular mechanisms underlying PUS7-mediated pseudouridylation remain unknown. A lack of targeted, high-throughput pseudouridine detection methods limits simultaneous interrogation of PUS7 regulatory features across many experimental conditions. We developed novel Nanopore sequencing tools, including Nano-Mod-Amp, to reveal pseudouridine stoichiometry, its RNA structural context, and dependence on PUS7 levels at specific sites across biological conditions. We established that RNA sequence and structural features are important for efficient mRNA modification by PUS7. Perturbing structure through mutations or antisense oligos modulates pseudouridylation levels. Pseudouridines are largely responsive to PUS7 protein levels, demonstrating the regulatory potential of varying PUS7 levels across cellular conditions. Conversely, PUS7 activity is also regulated in a cell-type specific manner, independent of PUS7 expression levels in a manner consistent with regulation by RNA structure and RNA binding proteins. Together, we uncovered regulatory features guiding PUS7 activity using new Nanopore sequencing tools, enabling site specific modulation of PUS7-dependent pseudouridines. Our framework can be applied to other RNA-modifying enzymes to query the regulation of the epitranscriptome.

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• Bulk RNA-seq atlas of cytokine-polarized murinebone-marrow-derived macrophages (BMDMs) across inflammatory, regulatory, and reparative stimuli
  GSE315641Mus musculus81 个样本2026-10-28

  Macrophages are highly plastic immune cells that adopt diverse functional states in response to local microenvironmental cues. In tissues, they contribute to host defense, maintain homeostasis, and coordinate responses to perturbations such as infection, injury, and inflammation. This functional diversity arises from their ability to integrate signals from cytokines, growth factors, and stromal interactions, particularly during tissue damage when macrophages transition from inflammatory to regulatory and reparative states. Despite increasing recognition of macrophage heterogeneity, most transcriptomic studies of macrophage polarization focus on a limited set of stimuli, providing an incomplete view of the cytokine-driven programs that shape macrophage behavior during inflammation and repair. Key mediators, including IL-4, IL-13, IL-33, IL-6, IL-10, GM-CSF, and TGF-β, induce distinct yet partially overlapping transcriptional responses that give rise to specialized and hybrid macrophage states. However, a systematic comparative analysis of these cytokine-induced programs remains lacking. To address this gap, we performed bulk RNA-sequencing of murine bone marrow–derived macrophages stimulated in vitro with a comprehensive panel of cytokines representing inflammatory, regulatory, and reparative pathways. This dataset enables direct comparison of cytokine-specific transcriptional programs, delineates classical, alternative, and hybrid activation states, and provides a resource for studying the molecular basis of macrophage plasticity.

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• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7
  GSE314741synthetic construct8 个样本2026-10-28

  Pseudouridines are abundant mRNA modifications that can impact splicing, translation, and stability to tune gene expression. PUS7 is one of the major mRNA pseudouridine synthases whose dysregulation leads to neurodevelopmental disorders and cancer, underscoring the critical function of PUS7-dependent pseudouridines. Beyond a short and degenerate consensus sequence, the molecular mechanisms underlying PUS7-mediated pseudouridylation remain unknown. A lack of targeted, high-throughput pseudouridine detection methods limits simultaneous interrogation of PUS7 regulatory features across many experimental conditions. We developed novel Nanopore sequencing tools, including Nano-Mod-Amp, to reveal pseudouridine stoichiometry, its RNA structural context, and dependence on PUS7 levels at specific sites across biological conditions. We established that RNA sequence and structural features are important for efficient mRNA modification by PUS7. Perturbing structure through mutations or antisense oligos modulates pseudouridylation levels. Pseudouridines are largely responsive to PUS7 protein levels, demonstrating the regulatory potential of varying PUS7 levels across cellular conditions. Conversely, PUS7 activity is also regulated in a cell-type specific manner, independent of PUS7 expression levels in a manner consistent with regulation by RNA structure and RNA binding proteins. Together, we uncovered regulatory features guiding PUS7 activity using new Nanopore sequencing tools, enabling site specific modulation of PUS7-dependent pseudouridines. Our framework can be applied to other RNA-modifying enzymes to query the regulation of the epitranscriptome.

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• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [endoBID]
  GSE314423Homo sapiens96 个样本2026-10-28

  Pseudouridines are abundant mRNA modifications that can impact splicing, translation, and stability to tune gene expression. PUS7 is one of the major mRNA pseudouridine synthases whose dysregulation leads to neurodevelopmental disorders and cancer, underscoring the critical function of PUS7-dependent pseudouridines. Beyond a short and degenerate consensus sequence, the molecular mechanisms underlying PUS7-mediated pseudouridylation remain unknown. A lack of targeted, high-throughput pseudouridine detection methods limits simultaneous interrogation of PUS7 regulatory features across many experimental conditions. We developed novel Nanopore sequencing tools, including Nano-Mod-Amp, to reveal pseudouridine stoichiometry, its RNA structural context, and dependence on PUS7 levels at specific sites across biological conditions. We established that RNA sequence and structural features are important for efficient mRNA modification by PUS7. Perturbing structure through mutations or antisense oligos modulates pseudouridylation levels. Pseudouridines are largely responsive to PUS7 protein levels, demonstrating the regulatory potential of varying PUS7 levels across cellular conditions. Conversely, PUS7 activity is also regulated in a cell-type specific manner, independent of PUS7 expression levels in a manner consistent with regulation by RNA structure and RNA binding proteins. Together, we uncovered regulatory features guiding PUS7 activity using new Nanopore sequencing tools, enabling site specific modulation of PUS7-dependent pseudouridines. Our framework can be applied to other RNA-modifying enzymes to query the regulation of the epitranscriptome.

  扰动筛选
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [incellSHAPEPool1]
  GSE314422Homo sapiens4 个样本2026-10-28

  Pseudouridines are abundant mRNA modifications that can impact splicing, translation, and stability to tune gene expression. PUS7 is one of the major mRNA pseudouridine synthases whose dysregulation leads to neurodevelopmental disorders and cancer, underscoring the critical function of PUS7-dependent pseudouridines. Beyond a short and degenerate consensus sequence, the molecular mechanisms underlying PUS7-mediated pseudouridylation remain unknown. A lack of targeted, high-throughput pseudouridine detection methods limits simultaneous interrogation of PUS7 regulatory features across many experimental conditions. We developed novel Nanopore sequencing tools, including Nano-Mod-Amp, to reveal pseudouridine stoichiometry, its RNA structural context, and dependence on PUS7 levels at specific sites across biological conditions. We established that RNA sequence and structural features are important for efficient mRNA modification by PUS7. Perturbing structure through mutations or antisense oligos modulates pseudouridylation levels. Pseudouridines are largely responsive to PUS7 protein levels, demonstrating the regulatory potential of varying PUS7 levels across cellular conditions. Conversely, PUS7 activity is also regulated in a cell-type specific manner, independent of PUS7 expression levels in a manner consistent with regulation by RNA structure and RNA binding proteins. Together, we uncovered regulatory features guiding PUS7 activity using new Nanopore sequencing tools, enabling site specific modulation of PUS7-dependent pseudouridines. Our framework can be applied to other RNA-modifying enzymes to query the regulation of the epitranscriptome.

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• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [invitroSHAPEPool1]
  GSE314421Homo sapiens2 个样本2026-10-28

  Pseudouridines are abundant mRNA modifications that can impact splicing, translation, and stability to tune gene expression. PUS7 is one of the major mRNA pseudouridine synthases whose dysregulation leads to neurodevelopmental disorders and cancer, underscoring the critical function of PUS7-dependent pseudouridines. Beyond a short and degenerate consensus sequence, the molecular mechanisms underlying PUS7-mediated pseudouridylation remain unknown. A lack of targeted, high-throughput pseudouridine detection methods limits simultaneous interrogation of PUS7 regulatory features across many experimental conditions. We developed novel Nanopore sequencing tools, including Nano-Mod-Amp, to reveal pseudouridine stoichiometry, its RNA structural context, and dependence on PUS7 levels at specific sites across biological conditions. We established that RNA sequence and structural features are important for efficient mRNA modification by PUS7. Perturbing structure through mutations or antisense oligos modulates pseudouridylation levels. Pseudouridines are largely responsive to PUS7 protein levels, demonstrating the regulatory potential of varying PUS7 levels across cellular conditions. Conversely, PUS7 activity is also regulated in a cell-type specific manner, independent of PUS7 expression levels in a manner consistent with regulation by RNA structure and RNA binding proteins. Together, we uncovered regulatory features guiding PUS7 activity using new Nanopore sequencing tools, enabling site specific modulation of PUS7-dependent pseudouridines. Our framework can be applied to other RNA-modifying enzymes to query the regulation of the epitranscriptome.

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• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [directRNA]
  GSE314420Homo sapiens7 个样本2026-10-28

  Pseudouridines are abundant mRNA modifications that can impact splicing, translation, and stability to tune gene expression. PUS7 is one of the major mRNA pseudouridine synthases whose dysregulation leads to neurodevelopmental disorders and cancer, underscoring the critical function of PUS7-dependent pseudouridines. Beyond a short and degenerate consensus sequence, the molecular mechanisms underlying PUS7-mediated pseudouridylation remain unknown. A lack of targeted, high-throughput pseudouridine detection methods limits simultaneous interrogation of PUS7 regulatory features across many experimental conditions. We developed novel Nanopore sequencing tools, including Nano-Mod-Amp, to reveal pseudouridine stoichiometry, its RNA structural context, and dependence on PUS7 levels at specific sites across biological conditions. We established that RNA sequence and structural features are important for efficient mRNA modification by PUS7. Perturbing structure through mutations or antisense oligos modulates pseudouridylation levels. Pseudouridines are largely responsive to PUS7 protein levels, demonstrating the regulatory potential of varying PUS7 levels across cellular conditions. Conversely, PUS7 activity is also regulated in a cell-type specific manner, independent of PUS7 expression levels in a manner consistent with regulation by RNA structure and RNA binding proteins. Together, we uncovered regulatory features guiding PUS7 activity using new Nanopore sequencing tools, enabling site specific modulation of PUS7-dependent pseudouridines. Our framework can be applied to other RNA-modifying enzymes to query the regulation of the epitranscriptome.

  扰动筛选
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [invitroSHAPEPool1]
  GSE314419Homo sapiens4 个样本2026-10-28

  Pseudouridines are abundant mRNA modifications that can impact splicing, translation, and stability to tune gene expression. PUS7 is one of the major mRNA pseudouridine synthases whose dysregulation leads to neurodevelopmental disorders and cancer, underscoring the critical function of PUS7-dependent pseudouridines. Beyond a short and degenerate consensus sequence, the molecular mechanisms underlying PUS7-mediated pseudouridylation remain unknown. A lack of targeted, high-throughput pseudouridine detection methods limits simultaneous interrogation of PUS7 regulatory features across many experimental conditions. We developed novel Nanopore sequencing tools, including Nano-Mod-Amp, to reveal pseudouridine stoichiometry, its RNA structural context, and dependence on PUS7 levels at specific sites across biological conditions. We established that RNA sequence and structural features are important for efficient mRNA modification by PUS7. Perturbing structure through mutations or antisense oligos modulates pseudouridylation levels. Pseudouridines are largely responsive to PUS7 protein levels, demonstrating the regulatory potential of varying PUS7 levels across cellular conditions. Conversely, PUS7 activity is also regulated in a cell-type specific manner, independent of PUS7 expression levels in a manner consistent with regulation by RNA structure and RNA binding proteins. Together, we uncovered regulatory features guiding PUS7 activity using new Nanopore sequencing tools, enabling site specific modulation of PUS7-dependent pseudouridines. Our framework can be applied to other RNA-modifying enzymes to query the regulation of the epitranscriptome.

  扰动筛选
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [invitroBIDpool2]
  GSE314391Homo sapiens8 个样本2026-10-28

  Pseudouridines are abundant mRNA modifications that can impact splicing, translation, and stability to tune gene expression. PUS7 is one of the major mRNA pseudouridine synthases whose dysregulation leads to neurodevelopmental disorders and cancer, underscoring the critical function of PUS7-dependent pseudouridines. Beyond a short and degenerate consensus sequence, the molecular mechanisms underlying PUS7-mediated pseudouridylation remain unknown. A lack of targeted, high-throughput pseudouridine detection methods limits simultaneous interrogation of PUS7 regulatory features across many experimental conditions. We developed novel Nanopore sequencing tools, including Nano-Mod-Amp, to reveal pseudouridine stoichiometry, its RNA structural context, and dependence on PUS7 levels at specific sites across biological conditions. We established that RNA sequence and structural features are important for efficient mRNA modification by PUS7. Perturbing structure through mutations or antisense oligos modulates pseudouridylation levels. Pseudouridines are largely responsive to PUS7 protein levels, demonstrating the regulatory potential of varying PUS7 levels across cellular conditions. Conversely, PUS7 activity is also regulated in a cell-type specific manner, independent of PUS7 expression levels in a manner consistent with regulation by RNA structure and RNA binding proteins. Together, we uncovered regulatory features guiding PUS7 activity using new Nanopore sequencing tools, enabling site specific modulation of PUS7-dependent pseudouridines. Our framework can be applied to other RNA-modifying enzymes to query the regulation of the epitranscriptome.

  扰动筛选
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [incellBIDPool1]
  GSE314389Homo sapiens66 个样本2026-10-28

  Pseudouridines are abundant mRNA modifications that can impact splicing, translation, and stability to tune gene expression. PUS7 is one of the major mRNA pseudouridine synthases whose dysregulation leads to neurodevelopmental disorders and cancer, underscoring the critical function of PUS7-dependent pseudouridines. Beyond a short and degenerate consensus sequence, the molecular mechanisms underlying PUS7-mediated pseudouridylation remain unknown. A lack of targeted, high-throughput pseudouridine detection methods limits simultaneous interrogation of PUS7 regulatory features across many experimental conditions. We developed novel Nanopore sequencing tools, including Nano-Mod-Amp, to reveal pseudouridine stoichiometry, its RNA structural context, and dependence on PUS7 levels at specific sites across biological conditions. We established that RNA sequence and structural features are important for efficient mRNA modification by PUS7. Perturbing structure through mutations or antisense oligos modulates pseudouridylation levels. Pseudouridines are largely responsive to PUS7 protein levels, demonstrating the regulatory potential of varying PUS7 levels across cellular conditions. Conversely, PUS7 activity is also regulated in a cell-type specific manner, independent of PUS7 expression levels in a manner consistent with regulation by RNA structure and RNA binding proteins. Together, we uncovered regulatory features guiding PUS7 activity using new Nanopore sequencing tools, enabling site specific modulation of PUS7-dependent pseudouridines. Our framework can be applied to other RNA-modifying enzymes to query the regulation of the epitranscriptome.

  扰动筛选
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [invitroBIDPool1]
  GSE314388Homo sapiens6 个样本2026-10-28

  Pseudouridines are abundant mRNA modifications that can impact splicing, translation, and stability to tune gene expression. PUS7 is one of the major mRNA pseudouridine synthases whose dysregulation leads to neurodevelopmental disorders and cancer, underscoring the critical function of PUS7-dependent pseudouridines. Beyond a short and degenerate consensus sequence, the molecular mechanisms underlying PUS7-mediated pseudouridylation remain unknown. A lack of targeted, high-throughput pseudouridine detection methods limits simultaneous interrogation of PUS7 regulatory features across many experimental conditions. We developed novel Nanopore sequencing tools, including Nano-Mod-Amp, to reveal pseudouridine stoichiometry, its RNA structural context, and dependence on PUS7 levels at specific sites across biological conditions. We established that RNA sequence and structural features are important for efficient mRNA modification by PUS7. Perturbing structure through mutations or antisense oligos modulates pseudouridylation levels. Pseudouridines are largely responsive to PUS7 protein levels, demonstrating the regulatory potential of varying PUS7 levels across cellular conditions. Conversely, PUS7 activity is also regulated in a cell-type specific manner, independent of PUS7 expression levels in a manner consistent with regulation by RNA structure and RNA binding proteins. Together, we uncovered regulatory features guiding PUS7 activity using new Nanopore sequencing tools, enabling site specific modulation of PUS7-dependent pseudouridines. Our framework can be applied to other RNA-modifying enzymes to query the regulation of the epitranscriptome.

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• Transcriptomic Insights into Cleidocranial Dysplasia Pathogenesis in Alveolar Bone Mesenchymal Stem Cells
  GSE297061Homo sapiens16 个样本2026-10-28

  Cleidocranial dysplasia (CCD) is a genetic disorder that primarily impacts skeletal and dental development, often leading to unerupted teeth due to impaired alveolar bone remodeling. This study investigates the transcriptomic profiles of alveolar bone-derived mesenchymal stem cells (aBMSCs) from CCD patients and unaffected controls to elucidate the molecular mechanisms underlying these dental defects. aBMSCs were isolated from two unrelated CCD patients with confirmed RUNX2 variants (c.673C>T, p.(Arg225Trp) and c.739delA, p.(Ser247Valfs*3)) and from 10 controls. Cells were cultured under general and osteogenic conditions. RNA sequencing, qRT-PCR, and bioinformatic analyses were used to assess gene expression profiles and validate key findings.CCDs exhibited significant dysregulation of ECM genes, including downregulation of COL1A1, COL3A1, and COL5A1 during osteogenic differentiation, indicating impaired bone formation. Disruptions in key signaling pathways, such as G protein-coupled receptor and prostaglandin signaling, highlighted broader osteogenic regulatory perturbations. CCDs displayed distinct transcriptional responses to osteogenic induction, with numerous DEGs, but no single gene was consistently dysregulated across all CCD-control comparisons, reflecting inter-individual heterogeneity. Notably, LGR4, PPP1R12B, PTGER2, and PTGS1 were consistently dysregulated in CCD under both basal and osteogenic conditions, with inverse expression relative to controls. These genes may represent key molecular signatures of CCD and contribute to its phenotypic variability. These findings highlight disrupted ECM formation and transcriptional heterogeneity in CCD, reflecting the complex effects of distinct RUNX2 variants. Consistently dysregulated genes, including LGR4, PPP1R12B, PTGER2, and PTGS1, may serve as key markers of impaired osteogenesis and potential therapeutic targets.

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• Micro-C-TALE: BAC-based targeted high-resolution measurement of 3D chromatin interactions [Micro-C-TALE]
  GSE351910Homo sapiens2 个样本2026-10-27

  Chromosome conformation capture methods have greatly advanced our understanding of genome organization, but obtaining high-resolution interaction maps of selected genomic regions remains costly due to the sequencing requirements. Here, we introduce Micro-C-TALE, a new chromosome conformation capture method that combines Micro-C, which uses micrococcal nuclease to the resolution and sensitivity of chromatin interaction measurements, and C-TALE, which uses probes generated from bacterial artificial chromosomes (BACs) for targeted enrichment. This combination enables the generation of high-resolution interaction maps without requiring custom synthesis of capture oligonucleotides. We applied Micro-C-TALE to a 214 kb region in human HAP1 cells, obtaining detailed interaction maps with approximately ~5-6 million sequenced read pairs. Compared with published genome-wide Micro-C data, Micro-C-TALE yielded a higher amount of informative interactions within the targeted region despite ~550-fold lower sequencing depth. To evaluate the sensitivity of the method to fine-scale changes in genome organization, we introduced a CTCF binding site into the targeted region using CRISPR-Cas9. Comparing Micro-C-TALE to the restriction enzyme-based C-TALE, we found Micro-C yielded a ~5-fold higher fraction of informative reads and detected novel CTCF-mediated point interactions associated with the inserted CTCF site, which were barely discernible using C-TALE. Our results demonstrate that Micro-C-TALE provides a flexible and cost-effective approach for targeted high-resolution measurement of chromatin interactions, facilitating the investigation of fine-scale genome organization and its response to genetic perturbations.

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• Micro-C-TALE: BAC-based targeted high-resolution measurement of 3D chromatin interactions [C-TALE]
  GSE351909Homo sapiens1 个样本2026-10-27

  Chromosome conformation capture methods have greatly advanced our understanding of genome organization, but obtaining high-resolution interaction maps of selected genomic regions remains costly due to the sequencing requirements. Here, we introduce Micro-C-TALE, a new chromosome conformation capture method that combines Micro-C, which uses micrococcal nuclease to the resolution and sensitivity of chromatin interaction measurements, and C-TALE, which uses probes generated from bacterial artificial chromosomes (BACs) for targeted enrichment. This combination enables the generation of high-resolution interaction maps without requiring custom synthesis of capture oligonucleotides. We applied Micro-C-TALE to a 214 kb region in human HAP1 cells, obtaining detailed interaction maps with approximately ~5-6 million sequenced read pairs. Compared with published genome-wide Micro-C data, Micro-C-TALE yielded a higher amount of informative interactions within the targeted region despite ~550-fold lower sequencing depth. To evaluate the sensitivity of the method to fine-scale changes in genome organization, we introduced a CTCF binding site into the targeted region using CRISPR-Cas9. Comparing Micro-C-TALE to the restriction enzyme-based C-TALE, we found Micro-C yielded a ~5-fold higher fraction of informative reads and detected novel CTCF-mediated point interactions associated with the inserted CTCF site, which were barely discernible using C-TALE. Our results demonstrate that Micro-C-TALE provides a flexible and cost-effective approach for targeted high-resolution measurement of chromatin interactions, facilitating the investigation of fine-scale genome organization and its response to genetic perturbations.

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• Genome-wide CRISPRi-seq profiling of essential-gene contributions to aminoglycoside susceptibility in Pseudomonas aeruginosa PAO1
  GSE349013Pseudomonas aeruginosa40 个样本2026-10-27

  This CRISPRi-seq dataset quantifies the abundance of 83,078 sgRNAs in a pooled Pseudomonas aeruginosa PAO1 CRISPRi library across untreated, aminoglycoside-treated and serum-containing conditions. Four independent experimental batches were used to measure untreated fitness, responses to tobramycin or amikacin, and fitness in 60% fetal bovine serum. The deposited processed data include raw guide counts and complete guide- and gene-level results for the predefined comparisons used in the study.

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• Microglial lipid signaling drives glioblastoma invasion and represents a therapeutic vulnerability
  GSE348401Mus musculus8 个样本2026-10-27

  Glioblastoma (GBM) is characterized by diffuse infiltration into the surrounding brain, limiting complete surgical resection, the strongest determinant of patient survival. The mechanisms driving this invasive growth remain incompletely understood. Here, we identify a lipid-mediated paracrine signaling axis through which tumor-associated microglia/macrophages promote glioma invasion. Integrating single-cell transcriptomics, spatial lipidomics, and functional perturbation across mouse models and human GBM samples, we show that invading tumor cells engage and reprogram myeloid cells via CSF1R–PI3K signaling. This induces lipid metabolic reprogramming and secretion of bioactive lipids, including lysophosphatidylcholines (LPCs) and lysophosphatidic acids (LPAs), which promote GBM invasion through distinct downstream pathways. Disruption of this myeloid–GBM axis, reduces lipid secretion and suppresses invasion. Targeting downstream LPA–LPAR or YAP/TAZ signaling further constrains invasion in a context-dependent manner. Together, these findings define a lipid-driven circuit linking the tumor microenvironment to glioma invasion and identify strategies to reduce infiltration and improve surgical resection.

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• Macrophage lipid signaling drives glioblastoma invasion and represents a therapeutic vulnerability
  GSE348147Mus musculus16 个样本2026-10-27

  Glioblastoma (GBM) is characterized by diffuse infiltration into the surrounding brain, limiting complete surgical resection, the strongest determinant of patient survival. The mechanisms driving this invasive growth remain incompletely understood. Here, we identify a lipid-mediated paracrine signaling axis through which tumor-associated microglia/macrophages promote glioma invasion. Integrating single-cell transcriptomics, spatial lipidomics, and functional perturbation across mouse models and human GBM samples, we show that invading tumor cells engage and reprogram myeloid cells via CSF1R–PI3K signaling. This induces lipid metabolic reprogramming and secretion of bioactive lipids, including lysophosphatidylcholines (LPCs) and lysophosphatidic acids (LPAs), which promote GBM invasion through distinct downstream pathways. Disruption of this myeloid–GBM axis, reduces lipid secretion and suppresses invasion. Targeting downstream LPA–LPAR or YAP/TAZ signaling further constrains invasion in a context-dependent manner. Together, these findings define a lipid-driven circuit linking the tumor microenvironment to glioma invasion and identify strategies to reduce infiltration and improve surgical resection.

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