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。

• A circRNA platform for safe partial reprogramming and rejuvenation of mesenchymal stem cells without pluripotent conversion
  GSE333770Homo sapiens9 个样本2026-10-28

  Mesenchymal stem cells (MSCs) are widely used in cell therapies; however, replicative senescence during in vitro expansion limits their potency and consistency. Partial reprogramming has emerged as a promising strategy to rejuvenate aged cells, yet concerns regarding unintended pluripotent conversion have hindered its translational application. Here we developed a circular RNA (circRNA)-based platform enabling safe partial reprogramming and rejuvenation of MSCs. We generated a lipid nanoparticle (LNP)-delivered circRNA co-expressing OCT4, SOX2, and KLF4 (circ-OSK) to achieve transient and coordinated expression of partial reprogramming factors without genomic modification in MSCs.
• Molecular mechanism of augmentation of oncogenic activity of MYC by TAF2 in HCC
  GSE329914Homo sapiens6 个样本2026-10-28

  The oncogenes MYC and TAF2 (TATA-box binding protein associated factor 2) are frequently overexpressed and co-amplified in many cancers, including Hepatocellular Carcinoma (HCC). We recently demonstrated that overexpression of TAF2 in mouse liver markedly augments MYC -induced HCC. MYC is a transcription factor. TAF2 is a component of transcription factor IID (TFIID) and functions as a transcription co-factor. We hypothesized that TAF2 modulates gene regulation by MYC, contributing to augmentation of MYC’s oncogenic activity. To test this hypothesis, we generated stable HepG2 cell lines overexpressing TAF2, MYC, or both. Combined overexpression significantly augmented in vitro proliferation, migration and invasion compared to the overexpression of either gene alone. We performed RNA-sequencing and CUT&RUN (cleavage under targets & release using nuclease) to identify MYC-regulated genes that are induced only by TAF2 overexpression. RASGEF1A (RasGEF domain family member 1A), a guanine exchange factor activating Ras, was significantly induced by TAF2 and MYC overexpression. Consequently, the MEK/ERK pathway was robustly activated in cells co-overexpressing TAF2 and MYC, rendering them uniquely sensitive to MEK inhibitor Trametinib. These findings suggest that HCC patients with TAF2 and MYC overexpression might benefit from targeted treatment with MEK inhibitors.
• Gene expression analysis of HepG2 cells overexpressing MYC or TAF2 and MYC
  GSE327282Homo sapiens6 个样本2026-10-28

  Taf2 is a transcription co-factor and a member of TFIID complex. MYC is a transcription factor. Overexpression of TAF2 markedly augments MYC-induced hepatocellular carcinoma (HCC) in mice. It is hypothesized that overexpression of TAF2 might modulate MYC-regulated gene expression and thereby increase oncogenic function of MYC. To test this hypothesis, we generated an in vitro system in which we established stable clones in HepG2 cells overexpressing MYC and both TAF2 and MYC (Hep-MYC and Hep-TAF2-MYC, respectively). The analysis shows that overexpression of TAF2 results in a significant increase in MYC-mediated expression of genes with oncogenic properties.
• Periplocin Targets Low Density Lipoprotein Receptor-Related Protein 4 and Protects Against Osteoarthritis
  GSE325883Homo sapiens9 个样本2026-10-28

  Osteoarthritis (OA) is recognized as the most common chronic joint disease, characterized primarily by the degeneration of articular cartilage. Periplocin, a cardiotonic steroid isolated from Periploca forrestii, has been proven to be involved in anti-inflammatory responses. However, the role and mechanism of periplocin in OA have not been confirmed.
• Nanostring transcriptomics profiling of wild type and PIK3CA knockin bladder cancer cells
  GSE323369Homo sapiens6 个样本2026-10-28

  Profiling of metabolic genes using nanostringtargeted transcriptomics to determine oncogenic metabolic rewiring of PIK3CA mutation in bladder cancer cells
• Impact of sacubitrilat-cGMP-PRKG1 signaling on microtubule detyrosination in cardiomyocytes
  GSE317137Homo sapiens8 个样本2026-10-28

  Microtubule detyrosination (dTyr-tub) and re-tyrosination (Tyr-tub) on the C-terminal residue of alpha-tubulin are mediated by the vasohibin (VASH)-small vasohibin-binding protein (SVBP) complex and tubulin tyrosine ligase (TTL), respectively. The level of dTyr-tub is elevated in heart failure (HF), and reducing this modification improves cardiac function, suggesting HF therapies may modulate it. We investigated whether components of the angiotensin receptor–neprilysin inhibitor LCZ696 affect dTyr-tub in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and explored the underlying mechanisms. Endothelin-1 (ET1) induced hypertrophy and increased dTyr-tub in wild-type but not in SVBP-deficient hiPSC-CMs and did not further enhance hypertrophy in TTL-deficient hiPSC-CMs. Both sacubitrilat and valsartan blocked ET1-induced hypertrophy, but only sacubitrilat prevented dTyr-tub accumulation. Sacubitrilat modestly stabilised atrial natriuretic peptide in culture medium, increased intracellular guanosine 3',5'-cyclic monophosphate (cGMP), augmented the phosphorylation of vasodilator stimulated phosphoprotein (Ser239), a substrate of cGMP-dependent protein kinase 1 (PRKG1), and lowered dTyr-tub level in hiPSC-CMs. Conversely, PRKG1 inhibition or knockdown increased dTyr-tub level. PRKG1A phosphorylated VASH1-WT but not a phosphomimetic VASH1 (VASH1-7E) in vitro. In addition, VASH1-7E did not interact with microtubules and did induce detyrosination. We overexpressed VASH1-WT, -7E and a dephosphorylated form of VASH1 (VASH1-7A) in newly generated VASH1-deficient hiPSC-CMs. The level of dTyr-tub was lower in VASH1-7E- than in VASH1-WT or VASH1-7A-expressing cells. In conclusion, sacubitrilat reduced dTyr-tub levels via PRKG1 activation and VASH1 phosphorylation, a mechanism that may contribute to the therapeutic benefit of LCZ696 in patients with HF.
• 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.

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• 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.

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• 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 [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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• RNA sequencing demonstrates alterations in the gene expression profile of HUVECs upon NETs stimulation.
  GSE314216Homo sapiens6 个样本2026-10-28

  RNA sequencing was applied to comprehensively assess changes in the gene expression profile of HUVECs following exposure to control or NETs.
• ACSS2-Mediated Metabolic-Epigenetic Crosstalk Drives Fulvestrant Resistance and Represents a Novel Therapeutic Target [NanoString]
  GSE300553Homo sapiens6 个样本2026-10-28

  Endocrine therapies target hormone-dependent cancer cells, primarily through estrogen receptor alpha (ERα), expressed in ~70% of breast cancers (ER+). Despite treatment advances, 30-40% of ER+ breast cancer patients experience recurrence and metastasis, with 5-year survival rates of only 31.9%. We validated poor outcomes for liver metastasis patients treated with Fulvestrant (Fulv) using the local Carle Foundation Hospital cohort and examined metabolic pathways in liver metastatic patient-derived xenograft (PDX) models, revealing upregulated lipid and acetyl-CoA production. Our previous work demonstrated that combining Fulv with acetyl-CoA synthase inhibitor (ACSI) targeting Acyl-CoA Synthetase Short Chain Family Member 2 (ACSS2), synergistically reduced ER+ metastatic breast cancer (MBC) cell viability in vitro. Using multiple analytical approaches—isotope tracing, CUT&RUN sequencing, immunofluorescence, western blot, and RNA sequencing—we characterized the effects of acetyl-CoA synthesis inhibition on Fulv-induced alterations. Results showed increased ACSS2 expression and acetate utilization with Fulv treatment. Isotope tracing revealed that Fulv decreased acetate flux to the TCA cycle while promoting fatty acid synthesis, though fatty acid synthesis inhibition did not synergize with Fulv. Importantly, ACSS2 was predominantly nuclear for therapy-resistant cells, suggesting epigenetic regulation roles. CUT&RUN sequencing showed Fulv treatment increased global ACSS2 binding sites and ERα/ACSS2/H3K27ac overlapping sites, which combination ACSI+Fulv therapy completely eliminated. RNA sequencing revealed increased cell proliferation gene expression with Fulv treatment. Combination therapy reduced metastatic burden. Our findings indicate ACSS2 contributes to endocrine therapy resistance through nuclear acetyl-CoA provision for epigenetic alterations. Targeting these cancer cell adaptations represents a novel therapeutic approach potentially reducing metastasis-related mortality and improving breast cancer treatment outcomes.
• Effect of stable knockdown of KRT18 on gene expression of SAS cells
  GSE292554Homo sapiens6 个样本2026-10-28

  KRT18 was reported to emerge at invasive front and was correlated to poor prognosis in oral squamous cell carcinoma. We extracted the RNA for sequencing from SAS cells which included that of wild type control groups and of stable KRT18 knockdown groups. From the results of GSEA analysis, the hallmark gene sets of epithelial mesenchymal transition (EMT) in KRT18 knockdown cells was highly suppressed. This implied that the emergence of KRT18 at invasive front of oral squamous cell carcinoma and the behavior of invasiveness of the cancer cells might be correlated to the process of EMT.
• Effect of PRAME overexpression on gene expression of A549 NSCLC cells
  GSE292191Homo sapiens4 个样本2026-10-28

  To investigate the function of PRAME in lung cancer, we established OE PRAME A549 cell line.
• Overexpression of desmin and vimentin in primary human bladder smooth muscle cells
  GSE127725Homo sapiens9 个样本2026-10-28

  Desmin and Vimentin overexpression differentially regulates smooth muscle gene expression in primary human bladder smooth muscle (HBSM) cells
• Transcriptome-wide mapping reveals an RNA-dependent mechanism of platinum cancer drugs. [ChIP-Seq_Spike-In]
  GSE352210Homo sapiens6 个样本2026-10-27

  Clinically used small molecules has been predicted to off-target to RNAs. However, the extend of this interaction is small molecule cancer therapeutics has not been characterized. Here, we screened for anticancer smalll molecules for their RNA interactions and uncovered widespread RNA off-targeting. Cisplatin was found to be one among the RNA binders. We used it as a model agent to identify the specific transcripts it interact with. To accomplish this, we developed Plat-RNAseq, a click-chemistry-mediated transcriptome-wide assay. Our results revealed that cisplatin binding was enriched at guanine-rich regions capable of forming RNA G-quadruplexes (rG4s) .We found that the recruitment of cisplatin to rG4s partially contributed to its cytotoxicity, revealing a noncanonical mechanism of action for this widely used chemotherapeutic agent. To assess the prevalence of RNA Pol II stalling in the cisplatin-target RNA we used RNA Pol II ChIP-seq and caculated the genome-wide stalling. This experiment uses RNA Pol II ChIP-seq with a Drosophila chromatin spike-in for quantitative normalization, unlike the previously deposited Pol II ChIP-seq (GSE309934), which was normalized to library size without a spike-in.
• GRHL2 loss alters redox homeostasis and attenuates erastin-induced ferroptosis in colorectal cancer cells
  GSE352117Homo sapiens6 个样本2026-10-27

  Redox homeostasis critically determines ferroptosis sensitivity, but the role of grainyhead-like 2 (GRHL2) in colorectal cancer remains unclear. RNA sequencing was performed to compare parental HCT116 cells with a CRISPR/Cas9-generated B8 GRHL2-KO clone and to define GRHL2-associated transcriptional changes relevant to redox homeostasis and ferroptosis sensitivity.
• 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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• Spatial transcriptomic profiling of human left ventricular tissue in ischaemic heart disease and dilated cardiomyopathy
  GSE351778Homo sapiens2 个样本2026-10-27

  Spatially resolved single-cell gene expression profiling was performed on fresh-frozen human left ventricular tissue from one ischaemic heart disease (IHD) and one dilated cardiomyopathy (DCM) specimen. The Xenium Human Multi-Tissue and Cancer Gene Expression panel supplemented with 100 custom probes was used to characterise cardiomyocytes and cardiac fibroblasts and investigate spatial relationships between fibroblast subpopulations and cardiomyocyte.

  单细胞空间转录组
• Study of LETT@MVs‑induced ferroptosis in tumor cells via supplementation of PUFA
  GSE351467Homo sapiens4 个样本2026-10-27

  Ferroptosis represents a promising therapeutic strategy for cancer, yet its anti‑tumor efficacy is largely limited by insufficient polyunsaturated fatty acids (PUFA) within the tumor microenvironment (TME). Aloe vera thylakoid membranes, naturally rich in PUFA, are an ideal source to facilitate robust lipid peroxidation. To address biological delivery obstacles, we constructed tumor‑targeting biomimetic microvesicles (LETT@MVs) by engineering aloe‑thylakoid‑derived microvesicles (TDMVs) with the multifunctional peptide LETT, which enables tumor‑targeted delivery and lysosomal escape. We systematically characterized the influences of LETT@MVs on hepatocellular carcinoma (HCC) cells, including cell viability, vasculogenic mimicry (VM) formation, lipid peroxidation and ferroptosis in vitro. Antitumor potency and biosafety were further validated using an orthotopic HCC mouse model. Mechanistically, multi‑omics strategies combining bulk RNA‑seq, metabolomics and scRNA‑seq were applied to decipher underlying molecular events. LETT@MVs were effectively internalized by HCC cells and successfully escaped lysosomal degradation. Taking advantage of endogenous PUFA stored in thylakoid components, LETT@MVs triggered potent lipid peroxidation and ferroptosis, meanwhile remodelled the extracellular matrix (ECM) to suppress vasculogenic mimicry. In orthotopic HCC mice, LETT@MVs markedly retarded tumor growth via ferroptosis induction and VM repression without obvious safety risks. Integrated multi‑omics data demonstrated that LETT@MVs rewired transcriptional and metabolic profiles of HCC cells, driving highly‑metabolic tumor cells toward ferroptotic stress status and generating near‑death cell subpopulations. Collectively, our work validates that aloe‑thylakoid‑originated biomimetic nanoplatform can trigger robust tumor ferroptosis through PUFA supplementation, providing new clues to conquer ferroptosis resistance and advance therapeutic interventions for hyper‑metabolic tumors.

  单细胞
• ScRNA-seq reveals cellular heterogeneity in urethral stricture
  GSE347480Homo sapiens6 个样本2026-10-27

  Urethral strictures are characterized by fibrotic scar tissue formation in the urethra, leading to difficulties in urination and potential renal dysfunction. The cellular microenvironment contributes to stenosis. However, the heterogeneity of key cell types hinders our understanding of this disease. Single-cell RNA sequencing was performed on three urethral scar tissues and three normal urethral tissues. First, the main cell types and sample heterogeneity were identified. Transcription factor (TF) and enrichment analyses were used to characterize the transcriptional regulation and metabolic patterns of fibroblasts and mast cells. Finally, CellChat was used to elucidate intercellular communication networks in urethral scar tissues. Of the eight cell types detected, fibroblasts, mast cells, and macrophages were major contributors to urethral scar tissue. These cells were categorized into seven (FB0–FB6), two (Mast0 and Mast1), and nine (Macro0-Macro8) subclusters, respectively, based on heterogeneity. Urethral scar tissue exhibited increased proportions of FB3 fibroblast, Mast1 mast cell, Macro1, and Macro7 counts. Marker genes of these subclusters facilitated the dysregulation of fibrosis through various biological processes, including cell adhesion and extracellular matrix organization. Additionally, screening of the dysregulation of multiple TFs and metabolic pathways revealed potential candidate TFs—ETS1 (from FB3) and SMAD3 (from Mast1)—associated with fibrosis. Furthermore, communication substantially increased between fibroblasts and other cells, and between Macro1 or Macro7 and other macrophage subclusters or fibroblasts in urethral scar tissue. We revealed the transcriptional characteristics of key cells involved in the fibrogenesis of urethral stricture, which elucidates the pathogenesis of urethral stenosis and advances the exploration of therapeutic targets.

  单细胞
• Hi-C analysis of HCT-116 and K562 cells
  GSE339260Homo sapiens2 个样本2026-10-27

  We performed Hi-C analysis on two common cancer cell lines.
• Single Cell multi-omics identifies VEGFA-mediated angiogenesis results in relapse in Sonic Hedgehog Medulloblastoma [Visium]
  GSE287107Homo sapiens6 个样本2026-10-27

  Relapse in Sonic Hegdehog Medulloblastoma (SHH-MB) a common pediatric brain tumor, remain a significant clinical challenge due to its poor prognosis and limited therapeutic intervention. Understanding the underlying molecular mechanisms driving relapse is critical for developing targeted interventions. Here, we utilize single-cell multi-omics, combining single-nucleus RNA sequencing (snRNA-seq), single-nucleus ATAC sequencing (snATAC-seq), and spatial omics to comprehensively characterize the cellular landscape and regulatory networks associated with SHH medulloblastoma relapse. Our integrative analysis identifies distinct GCP population enriched with angiogenic activity characterized high expression of Vascular Endothelial Growth Factor A (VEGFA) regulated by the transcription factor HIF1A. Notably, we find that VEGFA-mediated angiogenesis is a critical driver of tumor recurrence, promoting a microenvironment that supports tumor revascularization and growth in the endothelial cells. Furthermore, we uncover potential therapeutic targets within the VEGFA signaling axis that could disrupt angiogenesis and reduce relapse rates. Our findings provide new insights into the molecular and cellular dynamics of SHH medulloblastoma relapse and highlight VEGFA as a key mediator of angiogenesis-driven recurrence, offering a promising avenue for therapeutic intervention.

  单细胞空间转录组多组学
• Discovery of a novel inhibitor of macropinocytosis with antiviral activity
  GSE246407Homo sapiens6 个样本2026-10-27

  Several viruses hijack various forms of endocytosis in order to infect animal cells. Here, we report the discovery of a new molecule with antiviral properties, that we named virolin, which limits viral entry by macropinocitosis. The identification of virolin derives from a chemical screen using High-Throughput Microscopy, where we identified new chemical entities capable of preventing infection with a pseudotype virus expressing the spike (S) protein from SARS-CoV-2. Subsequent experiments confirmed the capacity of virolin to limit infection by actual SARS-CoV-2, as well as by additional viruses, such as Monkeypox or TBEV. Mechanistic analyses revealed that the compound inhibited macropinocytosis, limiting this entry route for the viruses. Importantly, virolin has no significant toxicity to host cells. In summary, we present a new molecule that inhibits viral entry via the endocytic route, offering a new alternative to prevent viral infection.
• Improvement of monoclonal antibody therapy against cancer through engineering stem cell-derived CD16-enhanced universal NKT cells (TCR)
  GSE352161Homo sapiens1 个样本2026-10-26

  Monoclonal antibody (mAb)-based therapies have revolutionized cancer treatment; however, their clinical efficacy is often limited by insufficient antibody-dependent cellular cytotoxicity (ADCC), tumor antigen escape, and an immunosuppressive tumor microenvironment (TME). To overcome these limitations, we developed an allogeneic stem cell-derived invariant natural killer T (NKT) cell platform engineered to express a high-affinity non-cleavable CD16 receptor (CD16HSC-NKT) for broad enhancement of mAb-based immunotherapy. Using a clinically guided differentiation platform, we generated highly pure and scalable CD16HSC-NKT cells exhibiting robust expression of NK receptors, potent cytotoxic machinery, and a Th1-biased cytokine profile. CD16HSC-NKT cells demonstrated potent intrinsic antitumor activity and potently enhanced the efficacy of multiple therapeutic antibodies, including Trastuzumab, Tafasitamab, Rituximab, Daratumumab, and Cusatuzumab, across diverse hematologic and solid tumor models. In vivo, combination therapy induced durable tumor eradication and prolonged survival in xenograft models, outperforming the clinically approved antibody-drug conjugate trastuzumab deruxtecan. Mechanistically, therapeutic antibodies promoted the expansion, persistence, and activation of CD16HSC-NKT cells within tumors. Importantly, CD16HSC-NKT uniquely remodeled the TME by selectively depleting CD1d-expressing tumor-associated macrophages and myeloid-derived suppressor cells. CD16HSC-NKT cells also exhibited minimal alloreactivity, no graft-versus-host disease, and no detectable systemic toxicity. Collectively, these findings establish CD16HSC-NKT cells as a safe, off-the-shelf cellular platform capable of broadly enhancing monoclonal antibody therapy through sustained ADCC, multimodal tumor targeting, and TME remodeling.
• BAP1 safeguards double-strand DNA break repair by limiting DNA end resection
  GSE351902Homo sapiens6 个样本2026-10-26

  The tumor suppressor BAP1 is frequently mutated in uveal melanoma and has been linked to homologous recombination (HR), yet how it influences DNA double-strand break (DSB) repair pathway choice remains unclear. Here, we identify BAP1 as a critical regulator that restricts DNA end resection to preserve non-homologous end-joining (NHEJ) capacity. Loss of BAP1 leads to aberrant accumulation of H2AK119 ubiquitination at DSBs, driving unscheduled resection in G1-phase cells and impairing recruitment of the anti-resection factor 53BP1. Co-depletion of the resection initiator CtIP restores NHEJ efficiency in BAP1-depleted cells, and pharmacological suppression of H2AK119 ubiquitination reverses these defects, placing unscheduled resection causally upstream of the end-joining failure. RNA sequencing and genome-wide H2AK119ub profiling show that neither the expression of NHEJ and HR genes nor the H2AK119ub landscape at their promoters is appreciably altered by BAP1 loss, supporting a role of altered H2AK119ub at the DSBs. These findings indicate that BAP1 safeguards DSB repair fidelity by preventing hyper-resection, thereby maintaining NHEJ competence. Consistent with this role, BAP1-depleted cells accumulate micronuclei, and BAP1 loss is associated with genomic instability in human uveal melanoma. Together, our results uncover a mechanism by which chromatin regulation constrains resection to coordinate repair pathway utilization.
• Molecular mapping of developing synovial fibroblasts in the TMJ reveals the crucial role of mechanical force in cavitation
  GSE351686Homo sapiens3 个样本2026-10-26

  The temporomandibular joint is formed from neural crest-derived mesenchyme with delayed development, distinct from other mesodermal derived majority synovial joints. Here, we perfomed spatial transcriptomics on human embryo samples at the initiation and cavitation stage from 9th , 10th and 11th post-conception weeks (PCW) to profile cellualr identity, singalling activity, extracellular matrix dynamics and ligand-receptor interactions during TMJ development. Our analysis has indicated the significant roles of synoival fibroblasts during the cavitation stage in the developing TMJ.

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