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。

• Cucumber-derived exosome-like nanovesicles promote diabetic wound healing via AKT-HO-1 signaling
  GSE318192Homo sapiens10 个样本2026-10-30

  This study investigates the therapeutic efficacy of Cucumis sativus-derived exosome-like nanovesicles (CELNs) in promoting diabetic wound healing. We identified CELNs as a superior candidate among Cucurbitaceae species for enhancing fibroblast function and modulating the wound microenvironment. RNA-seq analysis of CELN-treated human dermal fibroblasts reveals a significant upregulation of epigen (EPGN) and activation of the NRF2-mediated antioxidant pathway. Mechanistically, CELNs activate the EGFR–PI3K/AKT–NRF2 axis, which mitigates oxidative stress and accelerates cellular migration and proliferation. To ensure sustained delivery, a CELN-loaded hydrogel system was developed, which significantly enhanced re-epithelialization and collagen deposition in STZ-induced diabetic mice. Our findings demonstrate that CELNs offer a promising nanotherapeutic approach for managing chronic diabetic ulcers by targeting EGFR-mediated antioxidant signaling.
• Modeling Progressive Pseudorheumatoid Arthropathy of Childhood: Disease Progression and Cartilage Pathology in CCN6 Deficient Sheep
  GSE317805Ovis aries34 个样本2026-10-30

  Progressive Pseudorheumatoid Arthropathy of Childhood (PPAC) is a rare, autosomal recessive disorder caused by loss-of-function mutations in Cellular Communication Network Factor 6 (CCN6). Patients with PPAC present asymptomatic at birth but develop polyarticular arthropathy throughout childhood, often requiring multiple arthroplasties before age 30. Currently, no therapies exist to prevent or delay PPAC progression. Furthermore, the role of CCN6 in joint development and homeostasis is unknown due to the limited availability of pre-symptomatic patient tissue and the absence of any PPAC phenotype in Ccn6 knockout (KO) mice. CCN6 knockout sheep were generated, anticipating that a larger and longer-lived animal would better model human PPAC. We found that KO sheep were clinically indistinguishable from wild-type (WT) flock mates at birth but developed signs of joint disease that progressed with age. Macroscopic and histologic examination of KO tissues revealed evidence of cartilage damage that was absent in WT animals. KO and WT cartilage also differed transcriptomically, with KO sheep cartilage gene expression sharing multiple features observed in cartilage derived from PPAC-patient induced pluripotent cell lines. These data demonstrate that CCN6 knockout sheep recapitulate the key clinical, histological, and molecular features of human PPAC, establishing this model as a valuable platform for elucidating disease mechanisms and testing potential therapies.
• A Cross-scale Causal Mapping Framework Pinpoints Macrophage Orchestrators of Balanced Arterial Development
  GSE317047Homo sapiens3 个样本2026-10-30

  This dataset contains single-cell RNA sequencing profiles of induced pluripotent stem cell (iPSC)-derived blood vessel organoids (BVOs) cultured under different macrophage co-culture conditions. The aim is to investigate the regulation of vascular maturation and arterial development by the immune system. The BVOs were cultured either alone or with two polarized populations of iPSC-derived macrophages: activated (MGL low) and regenerative (MGL high). Single-cell transcriptomic analyses revealed polarization-dependent transcriptional changes in vascular endothelial and perivascular cell populations. This dataset allows for the identification of candidate genes and signaling pathways associated with arterial specification, vessel stabilization, and vascular maturation in a human organoid model.

  单细胞
• scRNAseq analysis of rat dorsal root ganglions from different peripheral injury treatment; a nerve transection, a crush 2 weeks after the cut and a resection of the neuroma 2 weeks afrer the initial cut
  GSE315353Rattus norvegicus6 个样本2026-10-30

  Peripheral nerve injury, whether caused by a cut, crush, or excessive stretch, can result in the formation of a painful neuroma at the site of damage. After a traumatic injury, regenerating nerves may develop a painful swelling at the severed end. This development is often accompanied by significant pain along the affected nerve's distribution, which can, in some cases, be more debilitating than the loss of motor function or sensation. It has been hypothesized that a proximal nerve crush may offer therapeutic benefits for painful neuromas by altering the axonal growth pattern and disrupting retrograde signaling. Despite existing treatment approaches, success in managing neuromas has been limited. Therefore, it is crucial to deepen our understanding of painful neuromas and develop more effective therapies. The molecular mechanisms underlying the formation and pain associated with symptomatic neuromas remain poorly understood. In this study, we thoroughly characterize the transcriptional changes in the dorsal root ganglion at single-cell resolution following proximal nerve crush versus nerve resection after neuronal transection.

  单细胞
• Immune cells adapt to distinct stem cell niches to govern tissue homeostasis [scRNA-seq]
  GSE314679Mus musculus2 个样本2026-10-30

  In adult tissues, epithelial stem cells exist within distinct residences, each endowing them with exclusive instructions for regenerative fitness in homeostasis and wound repair. Key components of these ‘niches’ are immune cells, which protect the host against external and internal threats. Whether and how stem cell: immune cell crosstalk contributes to normal tissue homeostasis remains less clear. Here, we discover functional adaptation of lymphocytes within two distinct skin stem cell niches and show that through this communication, each niche adjusts to meet diverse tissue demands. In the upper hair follicle, where microbial load is high, T cells express lymphotoxin-β and stimulate adjacent receptor-positive epithelial stem cells to form an immune-competent niche tailored to control microbial expansion. By contrast, in the epidermis, these T cells produce amphiregulin to maintain stem cell stoking of the skin’s barrier. Concomitantly, they express the immune checkpoint protein ‘LAG3’, which autorestricts lymphocyte numbers, and hence amphiregulin levels, thereby preventing over-proliferative responses. Finally, when epidermal T cells are absent, distinct dermal lymphocytes restore the imbalance by colonizing the niche and activating amphiregulin. Our findings unveil new modes of homeostatic control and functional specialization of immune-stem cell niches, tailoring them to suit the demands of distinct tissue microenvironments.

  单细胞
• Immune cells adapt to distinct stem cell niches to govern tissue homeostasis [bulkRNA-seq]
  GSE314678Mus musculus4 个样本2026-10-30

  In adult tissues, epithelial stem cells exist within distinct residences, each endowing them with exclusive instructions for regenerative fitness in homeostasis and wound repair. Key components of these ‘niches’ are immune cells, which protect the host against external and internal threats. Whether and how stem cell: immune cell crosstalk contributes to normal tissue homeostasis remains less clear. Here, we discover functional adaptation of lymphocytes within two distinct skin stem cell niches and show that through this communication, each niche adjusts to meet diverse tissue demands. In the upper hair follicle, where microbial load is high, T cells express lymphotoxin-β and stimulate adjacent receptor-positive epithelial stem cells to form an immune-competent niche tailored to control microbial expansion. By contrast, in the epidermis, these T cells produce amphiregulin to maintain stem cell stoking of the skin’s barrier. Concomitantly, they express the immune checkpoint protein ‘LAG3’, which autorestricts lymphocyte numbers, and hence amphiregulin levels, thereby preventing over-proliferative responses. Finally, when epidermal T cells are absent, distinct dermal lymphocytes restore the imbalance by colonizing the niche and activating amphiregulin. Our findings unveil new modes of homeostatic control and functional specialization of immune-stem cell niches, tailoring them to suit the demands of distinct tissue microenvironments.
• 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.

  扰动筛选SuperSeries
• The p38α MAPK-MK2 axis drives chemotherapy-mediated nuclear actin remodeling to promote ovarian cancer progression
  GSE311931Homo sapiens18 个样本2026-10-30

  We sequenced SKOV3 (EV), wild-type, and R62D cells treated with or without cisplatin.It is to figure out whether cisplatin and nuclear F-actin levels would affect the transcriptional profile.
• Acute Degradation of Pumilio Proteins Reveals a Biphasic Posttranscriptional Regulatory Hierarchy in Embryonic Stem Cell Fate Decision [RNA-Seq]
  GSE310694Mus musculus84 个样本2026-10-30

  Post-transcriptional regulation is critical for mammalian embryogenesis yet has been underexplored. We previously showed that RNA-binding Pumilio proteins (Pum1/2) are essential for early mouse embryogenesis and embryonic stem cell (ESC) functions. Here, using acute protein degradation systems combined with time-resolved RNA-seq and eCLIP, we delineate a two-phase regulatory hierarchy modulated by Pum1/2 in mouse ESCs. The first phase, occurring within 10 hours of Pum1/2 depletion, is predominantly the stabilization of over 100 Pum1/2-target mRNAs, while the second phase, occurring in subsequent 66 hours, propagates to over 1,000 mRNAs mostly through indirect regulatory effects. Functionally, Pum1/2 depletion delays transition from naïve to formative pluripotency, impairs neuroectoderm differentiation, and enhances germline specification. Mechanistically, Pum1/2 directly repress mRNAs encoding PRC2 subunits, including Suz12, thereby constraining H3K27me3 deposition at neuroectodermal gene loci. These findings establish Pum1/2 as biphasic post-transcriptional regulators of pluripotency and lineage balance and link RNA stability control to chromatin-mediated silencing.
• Acute Degradation of Pumilio Proteins Reveals a Biphasic Posttranscriptional Regulatory Hierarchy in Embryonic Stem Cell Fate Decision [iCLIP]
  GSE310693Mus musculus8 个样本2026-10-30

  Post-transcriptional regulation is critical for mammalian embryogenesis yet has been underexplored. We previously showed that RNA-binding Pumilio proteins (Pum1/2) are essential for early mouse embryogenesis and embryonic stem cell (ESC) functions. Here, using acute protein degradation systems combined with time-resolved RNA-seq and eCLIP, we delineate a two-phase regulatory hierarchy modulated by Pum1/2 in mouse ESCs. The first phase, occurring within 10 hours of Pum1/2 depletion, is predominantly the stabilization of over 100 Pum1/2-target mRNAs, while the second phase, occurring in subsequent 66 hours, propagates to over 1,000 mRNAs mostly through indirect regulatory effects. Functionally, Pum1/2 depletion delays transition from naïve to formative pluripotency, impairs neuroectoderm differentiation, and enhances germline specification. Mechanistically, Pum1/2 directly repress mRNAs encoding PRC2 subunits, including Suz12, thereby constraining H3K27me3 deposition at neuroectodermal gene loci. These findings establish Pum1/2 as biphasic post-transcriptional regulators of pluripotency and lineage balance and link RNA stability control to chromatin-mediated silencing.
• Ribosomal modification by BUD23 drives selective translational control over energy state and metabolic health [Ribo-seq]
  GSE308616Mus musculus4 个样本2026-10-30

  Efficient energy metabolism is essential for health, and its dysregulation drives cardiometabolic disease. Delivery of regulatory control through translation and ribosome function is emerging as important. Here, we identify the rRNA methyltransferase BUD23 as a potent regulator of cellular and systemic energy homeostasis. Adipocyte-specific deletion of BUD23 in mice regulates lipid and mitochondrial metabolism resulting in a pronounced lean phenotype and resistance to diet-induced obesity. Mechanistically, BUD23 modulates translation initiation and efficiency of mRNAs with specific features – including short 5’ UTR length and GC-rich post-initiation codon usage – characteristic of mitochondrial and lipogenic proteins.Together, our findings uncover a conserved translational control mechanism that regulates energy state in cellular metabolism.
• Ribosomal modification by BUD23 drives selective translational control over energy state and metabolic health
  GSE308532Mus musculus9 个样本2026-10-30

  Efficient energy metabolism is essential for health, and its dysregulation drives conditions like cardiometabolic disease and obesity. Delivery of regulatory control through translation and ribosome function is emerging as important. Here, we identify the rRNA methyltransferase BUD23 as a potent regulator of cellular and systemic energy homeostasis. Adipocyte-specific deletion of BUD23 in mice regulates lipid and mitochondrial metabolism resulting in a pronounced lean phenotype and resistance to diet-induced obesity. Mechanistically, BUD23 modulates translation initiation and efficiency of mRNAs with specific features – including short 5’ UTR length and GC-rich post-initiation codon usage - characteristic of mitochondrial and lipogenic proteins. Human genetic analyses and drug-target Mendelian Randomisation support a role for BUD23 in cardiometabolic traits and diseases. Together, our findings uncover a conserved translational control mechanism that regulates energy metabolism and offers a potential therapeutic target.
• Ribosomal modification by BUD23 drives selective translational control over energy state and metabolic health
  GSE308207Mus musculus16 个样本2026-10-30

  Efficient energy metabolism is essential for health, and its dysregulation drives conditions like cardiometabolic disease and obesity. Delivery of regulatory control through translation and ribosome function is emerging as important. Here, we identify the rRNA methyltransferase BUD23 as a potent regulator of cellular and systemic energy homeostasis. Adipocyte-specific deletion of BUD23 in mice regulates lipid and mitochondrial metabolism resulting in a pronounced lean phenotype and resistance to diet-induced obesity. Mechanistically, BUD23 modulates translation initiation and efficiency of mRNAs with specific features – including short 5’ UTR length and GC-rich post-initiation codon usage - characteristic of mitochondrial and lipogenic proteins. Human genetic analyses and drug-target Mendelian Randomisation support a role for BUD23 in cardiometabolic traits and diseases. Together, our findings uncover a conserved translational control mechanism that regulates energy metabolism and offers a potential therapeutic target.
• RHOX12L counteracts TRIM28-SETDB1 repression to activate embryonic IAP/MERVK retrotransposons [Embryo_Stranded_RNAseq]
  GSE307084Mus musculus样本未标注2026-10-30

  The onset of transcription in pre-implantation embryos includes the widespread transient activation of normally silenced endogenous retroviruses (ERVs) and other retrotransposons. In mice, DUX and OBOX transcription factors activate MERVL, but how other retrotransposons are activated remains largely unknown. Here, we identify RHOX12-like (RHOX12L) as a novel homeodomain-containing factor briefly activated by DUX in 2-cell embryos. Independent of specific DNA-binding activity, RHOX12L counteracts the general ERV repressor SETDB1 to transiently activate thousands of IAP/MERVK loci. Our biochemical studies reveal robust interaction of RHOX12L with SETDB1 as well as CBP/P300 and the BAF complex, concomitant with acetylation and chromatin opening at SETDB1-RHOX12L co-bound sites. In keeping, Rhox12l knockout embryos proved defective in IAP/MERVK activation. Furthermore, RHOX12L downregulates the OCT4 pluripotency network in embryonic stem cells (ESCs), potentially by sequestering OCT4 to de-repressed ERVs bearing upstream OCT4 binding sites. Taken together, we provide a mechanism for the strong, transient activation of the TRIM28/SETDB1-bound retrotransposon repertoire in pre-implantation embryos via co-activator tethering by RHOX12L.
• RHOX12L counteracts TRIM28-SETDB1 repression to activate embryonic IAP/MERVK retrotransposons [ATAC-Seq]
  GSE306939Mus musculus样本未标注2026-10-30

  The onset of transcription in pre-implantation embryos includes the widespread transient activation of normally silenced endogenous retroviruses (ERVs) and other retrotransposons. In mice, DUX and OBOX transcription factors activate MERVL, but how other retrotransposons are activated remains largely unknown. Here, we identify RHOX12-like (RHOX12L) as a novel homeodomain-containing factor briefly activated by DUX in 2-cell embryos. Independent of specific DNA-binding activity, RHOX12L counteracts the general ERV repressor SETDB1 to transiently activate thousands of IAP/MERVK loci. Our biochemical studies reveal robust interaction of RHOX12L with SETDB1 as well as CBP/P300 and the BAF complex, concomitant with acetylation and chromatin opening at SETDB1-RHOX12L co-bound sites. In keeping, Rhox12l knockout embryos proved defective in IAP/MERVK activation. Furthermore, RHOX12L downregulates the OCT4 pluripotency network in embryonic stem cells (ESCs), potentially by sequestering OCT4 to de-repressed ERVs bearing upstream OCT4 binding sites. Taken together, we provide a mechanism for the strong, transient activation of the TRIM28/SETDB1-bound retrotransposon repertoire in pre-implantation embryos via co-activator tethering by RHOX12L.
• RHOX12L counteracts TRIM28-SETDB1 repression to activate embryonic IAP/MERVK retrotransposons [2Cell_full_length_cDNA]
  GSE306936Mus musculus样本未标注2026-10-30

  The onset of transcription in pre-implantation embryos includes the widespread transient activation of normally silenced endogenous retroviruses (ERVs) and other retrotransposons. In mice, DUX and OBOX transcription factors activate MERVL, but how other retrotransposons are activated remains largely unknown. Here, we identify RHOX12-like (RHOX12L) as a novel homeodomain-containing factor briefly activated by DUX in 2-cell embryos. Independent of specific DNA-binding activity, RHOX12L counteracts the general ERV repressor SETDB1 to transiently activate thousands of IAP/MERVK loci. Our biochemical studies reveal robust interaction of RHOX12L with SETDB1 as well as CBP/P300 and the BAF complex, concomitant with acetylation and chromatin opening at SETDB1-RHOX12L co-bound sites. In keeping, Rhox12l knockout embryos proved defective in IAP/MERVK activation. Furthermore, RHOX12L downregulates the OCT4 pluripotency network in embryonic stem cells (ESCs), potentially by sequestering OCT4 to de-repressed ERVs bearing upstream OCT4 binding sites. Taken together, we provide a mechanism for the strong, transient activation of the TRIM28/SETDB1-bound retrotransposon repertoire in pre-implantation embryos via co-activator tethering by RHOX12L.
• RHOX12L counteracts TRIM28-SETDB1 repression to activate embryonic IAP/MERVK retrotransposons [mESC_RNAseq]
  GSE306934Mus musculus样本未标注2026-10-30

  The onset of transcription in pre-implantation embryos includes the widespread transient activation of normally silenced endogenous retroviruses (ERVs) and other retrotransposons. In mice, DUX and OBOX transcription factors activate MERVL, but how other retrotransposons are activated remains largely unknown. Here, we identify RHOX12-like (RHOX12L) as a novel homeodomain-containing factor briefly activated by DUX in 2-cell embryos. Independent of specific DNA-binding activity, RHOX12L counteracts the general ERV repressor SETDB1 to transiently activate thousands of IAP/MERVK loci. Our biochemical studies reveal robust interaction of RHOX12L with SETDB1 as well as CBP/P300 and the BAF complex, concomitant with acetylation and chromatin opening at SETDB1-RHOX12L co-bound sites. In keeping, Rhox12l knockout embryos proved defective in IAP/MERVK activation. Furthermore, RHOX12L downregulates the OCT4 pluripotency network in embryonic stem cells (ESCs), potentially by sequestering OCT4 to de-repressed ERVs bearing upstream OCT4 binding sites. Taken together, we provide a mechanism for the strong, transient activation of the TRIM28/SETDB1-bound retrotransposon repertoire in pre-implantation embryos via co-activator tethering by RHOX12L.
• RHOX12L counteracts TRIM28-SETDB1 repression to activate embryonic IAP/MERVK retrotransposons [KO_embryo_RNAseq]
  GSE306927Mus musculus样本未标注2026-10-30

  The onset of transcription in pre-implantation embryos includes the widespread transient activation of normally silenced endogenous retroviruses (ERVs) and other retrotransposons. In mice, DUX and OBOX transcription factors activate MERVL, but how other retrotransposons are activated remains largely unknown. Here, we identify RHOX12-like (RHOX12L) as a novel homeodomain-containing factor briefly activated by DUX in 2-cell embryos. Independent of specific DNA-binding activity, RHOX12L counteracts the general ERV repressor SETDB1 to transiently activate thousands of IAP/MERVK loci. Our biochemical studies reveal robust interaction of RHOX12L with SETDB1 as well as CBP/P300 and the BAF complex, concomitant with acetylation and chromatin opening at SETDB1-RHOX12L co-bound sites. In keeping, Rhox12l knockout embryos proved defective in IAP/MERVK activation. Furthermore, RHOX12L downregulates the OCT4 pluripotency network in embryonic stem cells (ESCs), potentially by sequestering OCT4 to de-repressed ERVs bearing upstream OCT4 binding sites. Taken together, we provide a mechanism for the strong, transient activation of the TRIM28/SETDB1-bound retrotransposon repertoire in pre-implantation embryos via co-activator tethering by RHOX12L.
• RHOX12L counteracts TRIM28-SETDB1 repression to activate embryonic IAP/MERVK retrotransposons [CUT&Tag]
  GSE306922Mus musculus样本未标注2026-10-30

  The onset of transcription in pre-implantation embryos includes the widespread transient activation of normally silenced endogenous retroviruses (ERVs) and other retrotransposons. In mice, DUX and OBOX transcription factors activate MERVL, but how other retrotransposons are activated remains largely unknown. Here, we identify RHOX12-like (RHOX12L) as a novel homeodomain-containing factor briefly activated by DUX in 2-cell embryos. Independent of specific DNA-binding activity, RHOX12L counteracts the general ERV repressor SETDB1 to transiently activate thousands of IAP/MERVK loci. Our biochemical studies reveal robust interaction of RHOX12L with SETDB1 as well as CBP/P300 and the BAF complex, concomitant with acetylation and chromatin opening at SETDB1-RHOX12L co-bound sites. In keeping, Rhox12l knockout embryos proved defective in IAP/MERVK activation. Furthermore, RHOX12L downregulates the OCT4 pluripotency network in embryonic stem cells (ESCs), potentially by sequestering OCT4 to de-repressed ERVs bearing upstream OCT4 binding sites. Taken together, we provide a mechanism for the strong, transient activation of the TRIM28/SETDB1-bound retrotransposon repertoire in pre-implantation embryos via co-activator tethering by RHOX12L.
• Transcriptomic response to TRIP12 knockdown and HSP90 inhibition in melanoma cells
  GSE306539Homo sapiens32 个样本2026-10-30

  Melanoma, as a typical cancer, is characterized by high mutational burden and rapid proliferation, both of which contribute to elevated proteotoxic stress and reliance on protein quality control systems. To model this, we used the melanoma cell lines Ma-Mel-102 (differentiated, MLANA- and MITF-expressing, ~1200 missense mutations) and Ma-Mel-94 (dedifferentiated, ~700 missense mutations). This study investigates the role of the E3 ubiquitin ligase TRIP12 in regulating proteostasis in melanoma, particularly under proteotoxic stress induced by inhibition of HSP90, a key molecular chaperone. This dataset provides RNA-seq transcriptomic profiles of Ma-Mel-94 and Ma-Mel-102 cells following siRNA-mediated TRIP12 knockdown, with or without HSP90 inhibition by 17-DMAG.
• 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.

  扰动筛选
• iPSC-derived antigen-presenting cells engineered to express IL12 stimulate tumor-tissue reprogramming and antitumor immunity
  GSE303722Homo sapiens; Mus musculus64 个样本2026-10-30

  Activation of cancer-reactive T cells by dendritic cells (DCs) is important for cancer elimination by host immunity. One type of cancer immunotherapy in which DCs loaded with "cancer antigens" are administered has not been able to achieve stable efficacy due to heterogeneity in cell quality dependent on patient DC status. We constructed IL12-producing antigen-presenting cells from mouse induced pluripotent stem cells (iPSC). These cells can be controlled to proliferate using cytokines, allowing for the mass production of cells with stable performance. When these cells were loaded with a model cancer antigen and administered to cancer-bearing mice, cancer-reactive T cells rapidly acquired effector functions and propagated an interferon (IFN)-stimulated gene signature to cancer tissue distant from the site of administration. This was accompanied by infiltration of effector cells into the cancer tissue, while associated with a decrease in myeloid-derived suppressor cells. These were extremely more potent than immune checkpoint inhibitors (ICIs) and were further amplified in combination with ICIs and correlated with antitumor effects. Based on these observations, we constructed IL12-producing antigen-presenting cells from human iPSCs that express only HLA molecules involved in cancer antigen presentation and exclude other HLA molecules for improved versatility. These human cells, like their mouse counterparts, were capable of cytokine-regulated proliferation and induced antigen-specific activation and IFN-γ production of cancer antigen-specific T cells. Thus, these cells may become an alternative antigen-presenting cell platform for patient DCs to overcome HLA polymorphisms and ensure stable supply and quality.
• Multi-lineage evolution of drug resistance via a keratin 17+ aberrant basaloid drug tolerant persister population in EGFR-mutant NSCLC
  GSE303284Homo sapiens6 个样本2026-10-30

  We have an incomplete understanding of how EGFR-mutant drug tolerant persister cells (DTPCs) adapt to tolerate EGFR signaling blockade and whether these different mechanisms of resistance are present at baseline or emerge from a common DTPC population. In this study, we leveraged single cell RNA sequencing to comprehensively characterize phenotypes potentiating EGFR-mutant DTPCs and minimal residual disease states in part by sampling in vitro model systems. Using this and other single cell RNA sequencing data, we uncovered that a recurrent, novel KRT17+/KRT5- DTPC population harboring basaloid features and decreased alveolar lineage fidelity could give rise to diverse, multilineage mechanisms of targeted therapy resistance.

  单细胞
• 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.

  扰动筛选
• 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
• Transcriptomic Changes of C.elegans in Subaqueous Acoustic Levitation Microgravity Device Artificial (Microgravity Environment).
  GSE301015Caenorhabditis elegans6 个样本2026-10-30

  To investigate the effects of a microgravity environment generated by the Subaqueous Acoustic Levitation Microgravity Device (SALMD) on biological systems, Caenorhabditis elegans were utilized as a model organism. A total of 8,000 C. elegans were cultured under standard conditions as the control group, while another 8,000 were cultured in microgravity environment via SALMD for 24 hours as the experimental group. Following exposure, the organisms were sacrificed for RNA extraction, and transcriptomic analysis was performed using bulk RNA sequencing.
• Nuclear corepressors NCOR1 and NCOR2 entrain thymocyte signaling, selection, and emigration [scATAC-seq]
  GSE297937Mus musculus2 个样本2026-10-30

  T cell development progresses through discrete stages that require precise control of gene activation and gene repression. Gene silencing is primarily mediated through epigenetic modifications, mediated by the interaction of transcription factors with repressor complexes containing chromatin-remodeling enzymes. Found within many such complexes, the corepressors NCOR1 and NCOR2 recruit histone deacetylases to suppress transcription of target genes. Using Cd4-cre mice, we identified multiple roles for NCOR1 and NCOR2 throughout thymocyte development. Here, we employed scATAC-seq to examine whether the RNA- and protein-level differences observed in these mice correlate with changes in chromatin accessibility.

  单细胞
• Heightened DOT1L-AF10 enriches H3K79me3 to promote pro-atherogenic inflammatory endothelial phenotype through NF-κB p65
  GSE295366Homo sapiens3 个样本2026-10-30

  DOT1L-catalyzed H3K79 methylation is a hallmark of actively transcribed genes and has been extensively studied in developmental and disease contexts. While DOT1L inhibition has emerged as a promising therapeutic strategy in cancer, its role in pro-atherogenic endothelial inflammation remains unclear. To investigate this, we utilized an in vivo partial carotid artery ligation model and observed increased DOT1L expression and H3K79me3 level. Consistently, in vitro studies employing a 3D-printed human coronary artery model and TNF-α stimulation corroborated these results, showing elevated DOT1L expression and H3K79me3 deposition, while levels of H3K79me and me2 remained unchanged. Further analyses identified key DotCom complex components, AF10 and AF9 (upregulated) and AF17 (downregulated), as contributors to the enhanced H3K79me3 landscape. CUT&RUN sequencing showed prominent H3K79me3 enrichment at the RELA (NF-κB p65) promoter, corresponding with increased NF-κB p65 expression and activation. Notably, inhibition/knockdown of the methyltransferase DOT1L or overexpression of the demethylase FBXL10 significantly reduced H3K79me3 levels, thereby suppressing NF-κB p65 expression and attenuating endothelial inflammation, independent of canonical NF-κB p65 activation. These findings establish DOT1L-mediated H3K79me3 as a crucial epigenetic regulator of endothelial inflammation, highlighting a potential therapeutic avenue for mitigating NF-κB p65-driven pro-atherogenic endothelial dysfunction.
• AR-V7 condensates drive androgen-independent transcription in castration resistant prostate cancer
  GSE292445Homo sapiens6 个样本2026-10-30

  Biomolecular condensates organize cellular environments and regulate key processes like transcription. We previously showed that full-length androgen receptor (AR-FL), a major oncogenic driver in prostate cancer (PCa), forms nuclear condensates upon androgen stimulation in androgen-sensitive PCa cells. Disrupting these condensates impairs AR-FL transcriptional activity, highlighting their importance. However, resistance to androgen deprivation therapy often leads to castration-resistant prostate cancer (CRPC), driven by constitutively active splice variants like AR variant 7 (AR-V7). The mechanisms underlying AR-V7’s role in CRPC remain unclear. We characterized AR-V7’s condensate-forming ability and compared its phase behavior with AR- FL across PCa models and in vitro. Our findings indicate that cellular context influences AR-V7’s condensate formation. Unlike AR-FL, AR-V7 spontaneously forms condensates without androgen stimulation and functions independently of AR-FL in CRPC. However, AR-V7 requires a higher concentration to form condensates in cells and in vitro. We reveal that AR-V7 drives transcription through condensate-dependent and independent mechanisms. Using an AR-V7 mutant incapable of forming condensates but retaining nuclear localization and DNA binding, we show the condensate-dependent regime activates part of the oncogenic KRAS pathway in CRPC. Genes under this regime harbored more AR-binding sites and exhibited boosted expression in response to AR-V7. These findings uncover AR-V7 condensates’ role in oncogenic transcription and CRPC progression.
• Lymphatic endothelium-restricted synthetic circuit therapy potentiates repair and chemoimmunotherapy response in a surgical lymphedema model
  GSE285323Mus musculus9 个样本2026-10-30

  Lymphedema is a frequent and difficult-to-treat surgical complication of various cancers involving lymph node dissection. Lymphangiogenic factor therapy is not clinically applied due to its pro-tumor effects. Here, our pharmacodynamic analysis and lymphovenous anastomosis intervention show that lymphedema is associated with reduced antitumor immunity in breast cancer patients. AAV delivery of lymphangiogenic factors mediated by Prox1, a LEC promoter, promotes tumor progression because of aberrant Prox1 activities in tumor cells. Therefore, we develop a LEC-specific synthetic circuit, LNCSMD, by adding staufen1-mediated mRNA decay (SMD) elements corresponding to high-throughput-identified tumor-specific lncRNAs. LNCSMD treatment abolishes unwanted outputs in tumor cells, induces lymphatic vessel repair and potentiates chemoimmunotherapy in vivo. We uncover that SMD can be harnessed as off-the-shelf synthetic circuit treatment for lymphedema.