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。

• Pervasive ERBB2 amplification and immune exclusion characterize esophageal adenocarcinoma brain metastases with divergent clinical outcomes
  GSE346866Homo sapiens74 个样本2026-10-26

  Esophageal adenocarcinoma (EAC) is an aggressive malignancy with increasing incidence in younger adults. Brain metastases occur in a clinically significant subset of patients and carry a median survival of 14 months, yet the genomic drivers, mechanisms of seeding, and the basis for rare long-term survival remain undefined. Overall, our work establishes ERBB2 amplification architecture as a major determinant of survival in EAC brain metastasis and demonstrates that HER2 IHC alone is insufficient for risk stratification. We propose DNA-level ERBB2 assessment, including in HER2 IHC 3+ cases, and early brain surveillance in HER2-positive primary EAC to guide therapy selection and enable timely intervention.
• TNFR2 agonism increases tissue and effector Treg cells
  GSE344965Mus musculus12 个样本2026-10-26

  Autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus are driven by chronic inflammation and tissue damage. Regulatory T (Treg) cells are critical for maintaining immune tolerance, yet their therapeutic use is limited by stability and tissue homing. Here, we demonstrate that agonism of tumor necrosis factor receptor 2 (TNFR2) increases effector and tissue-competent Treg cell progenitors in mice and humans. Single-cell RNA sequencing reveals that TNFR2 is highly expressed on early and late non-lymphoid tissue Treg cell precursors, with expression strongly correlated with the BATF-driven tissue Treg cell transcriptional program. In vivo, a single dose of TNFR2 agonist promotes the clonal commitment of Treg cells to effector and tissue lineage, increasing tissue Treg cell populations in lymphoid and peripheral tissues. This increase is associated with enhanced suppressive function, epigenetic stability (preserved FOXP3 CNS2 demethylation), and resistance to inflammatory conversion. In murine models of skin inflammation and experimental autoimmune encephalomyelitis, TNFR2 agonism ameliorates disease severity in a dose-dependent manner. Critically, in human Treg cells, TNFR2 agonism induces elements of the tissue residency transcriptional program—including upregulation of LAYN, CCR8, CCR4 and TIGIT—while maintaining lineage stability. These findings establish TNFR2 signaling as a central driver of effector and tissue Treg cell differentiation and position TNFR2 agonism as a transformative strategy for generating stable, tissue-competent effector Treg cells as a promising immunomodulatory therapy for autoimmune and inflammatory diseases.

  单细胞
• Recordanelles for transcriptome-wide single-cell RNA recording in human cells [dataset_2 RNA-Seq]
  GSE344934Homo sapiens48 个样本2026-10-26

  Transcriptomic measurement technologies provide powerful approaches to understand biology but are limited to providing either a high-resolution snapshot at a moment in time or a low-resolution history of transcription constrained to a few genes over a narrow time range. Here, we introduce the “recordanelle”, a single-component synthetic organelle capable of recording the transcriptome in human cells. Recordanelles are composed of a mitochondrial membrane anchor, a condensate assembler and a poly-A-binding protein. We demonstrate that the recordanelle can be engineered to recruit engineered RNAs or a sampling of up to 90% of all endogenous mRNAs and protect them over several days. We further show that transient and dynamic transcriptional responses resulting from inducible promoters or interferon signaling are preserved throughout time within the recordanelle at the single-cell level. This work provides a non-disruptive and unbiased transcriptome-wide single-cell RNA recording technology to enable a deeper understanding of biology.

  单细胞
• Recordanelles for transcriptome-wide single-cell RNA recording in human cells [dataset_4 scRNA-seq]
  GSE344737Homo sapiens2 个样本2026-10-26

  Transcriptomic measurement technologies provide powerful approaches to understand biology but are limited to providing either a high-resolution snapshot at a moment in time or a low-resolution history of transcription constrained to a few genes over a narrow time range. Here, we introduce the “recordanelle”, a single-component synthetic organelle capable of recording the transcriptome in human cells. Recordanelles are composed of a mitochondrial membrane anchor, a condensate assembler and a poly-A-binding protein. We demonstrate that the recordanelle can be engineered to recruit engineered RNAs or a sampling of up to 90% of all endogenous mRNAs and protect them over several days. We further show that transient and dynamic transcriptional responses resulting from inducible promoters or interferon signaling are preserved throughout time within the recordanelle at the single-cell level. This work provides a non-disruptive and unbiased transcriptome-wide single-cell RNA recording technology to enable a deeper understanding of biology.

  单细胞
• Recordanelles for transcriptome-wide single-cell RNA recording in human cells [dataset_3 RNA-Seq]
  GSE344736Homo sapiens50 个样本2026-10-26

  Transcriptomic measurement technologies provide powerful approaches to understand biology but are limited to providing either a high-resolution snapshot at a moment in time or a low-resolution history of transcription constrained to a few genes over a narrow time range. Here, we introduce the “recordanelle”, a single-component synthetic organelle capable of recording the transcriptome in human cells. Recordanelles are composed of a mitochondrial membrane anchor, a condensate assembler and a poly-A-binding protein. We demonstrate that the recordanelle can be engineered to recruit engineered RNAs or a sampling of up to 90% of all endogenous mRNAs and protect them over several days. We further show that transient and dynamic transcriptional responses resulting from inducible promoters or interferon signaling are preserved throughout time within the recordanelle at the single-cell level. This work provides a non-disruptive and unbiased transcriptome-wide single-cell RNA recording technology to enable a deeper understanding of biology.

  单细胞
• CCL11 regulates microglial responses in aged mice following ICH.
  GSE344735Mus musculus6 个样本2026-10-26

  CCL11 level increases in circulation with age, with the ability to penetrate the brain, where it attenuates homeostatic functions. Microglia (MG) are essential brain tissue macrophages, and are critical for improved ICH outcomes. To study the effect of systemic-neutralization of CCL11 in aged mice, particularly on MG gene expression changes following ICH injury, we performed RNA-sequencing of MG collected after experimental ICH in a mouse blood injection model. We intraperitoneally administered an anti-CCL11 antibody to aged male mice prior to ICH, isolated MG from the ipsilateral hemisphere, and used the MG for bulk RNA-sequencing analysis. We found that sequestration of CCL11 in the circulation of aged mice prior to ICH upregulates the expression of microglial genes linked to pro-phagocytic, anti-oxidative, and anti-inflammatory signaling.
• Recordanelles for transcriptome-wide single-cell RNA recording in human cells [dataset_1 RNA-Seq]
  GSE344731Homo sapiens60 个样本2026-10-26

  Transcriptomic measurement technologies provide powerful approaches to understand biology but are limited to providing either a high-resolution snapshot at a moment in time or a low-resolution history of transcription constrained to a few genes over a narrow time range. Here, we introduce the “recordanelle”, a single-component synthetic organelle capable of recording the transcriptome in human cells. Recordanelles are composed of a mitochondrial membrane anchor, a condensate assembler and a poly-A-binding protein. We demonstrate that the recordanelle can be engineered to recruit engineered RNAs or a sampling of up to 90% of all endogenous mRNAs and protect them over several days. We further show that transient and dynamic transcriptional responses resulting from inducible promoters or interferon signaling are preserved throughout time within the recordanelle at the single-cell level. This work provides a non-disruptive and unbiased transcriptome-wide single-cell RNA recording technology to enable a deeper understanding of biology.

  单细胞
• TNFR2 agonism increases tissue and effector Treg cells
  GSE344625Mus musculus2 个样本2026-10-26

  Autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus are driven by chronic inflammation and tissue damage. Regulatory T (Treg) cells are critical for maintaining immune tolerance, yet their therapeutic use is limited by stability and tissue homing. Here, we demonstrate that agonism of tumor necrosis factor receptor 2 (TNFR2) increases effector and tissue-competent Treg cell progenitors in mice and humans. Single-cell RNA sequencing reveals that TNFR2 is highly expressed on early and late non-lymphoid tissue Treg cell precursors, with expression strongly correlated with the BATF-driven tissue Treg cell transcriptional program. In vivo, a single dose of TNFR2 agonist promotes the clonal commitment of Treg cells to effector and tissue lineage, increasing tissue Treg cell populations in lymphoid and peripheral tissues. This increase is associated with enhanced suppressive function, epigenetic stability (preserved FOXP3 CNS2 demethylation), and resistance to inflammatory conversion. In murine models of skin inflammation and experimental autoimmune encephalomyelitis, TNFR2 agonism ameliorates disease severity in a dose-dependent manner. Critically, in human Treg cells, TNFR2 agonism induces elements of the tissue residency transcriptional program—including upregulation of LAYN, CCR8, CCR4 and TIGIT—while maintaining lineage stability. These findings establish TNFR2 signaling as a central driver of effector and tissue Treg cell differentiation and position TNFR2 agonism as a transformative strategy for generating stable, tissue-competent effector Treg cells as a promising immunomodulatory therapy for autoimmune and inflammatory diseases.

  单细胞
• Effect of TNFR2 agonism on CD4+ T cells (single-cell level) from healthy and SLE donors
  GSE344526Homo sapiens35 个样本2026-10-26

  We treated peripheral blood mononuclear cells from healthy donors and systemic lupus erythematosus (SLE) patients with (i) a human-specific tetravalent VHH-Fc fusion TNFR2 agonist, (ii) isotope control VHH and (iii) an IL2-mutein.

  单细胞
• Transcriptomic profiling of C17orf58 knockdown in Jurkat T cells
  GSE343757Homo sapiens9 个样本2026-10-26

  C17orf58 is a poorly characterized gene implicated in the survival and proliferation of T-cell malignancies. To characterize transcriptional changes associated with C17orf58 depletion, RNA sequencing was performed in Jurkat T cells following lentiviral transduction with shRNAs targeting C17orf58. Two independent C17orf58-targeting shRNA constructs were evaluated, with scrambled shRNA and luciferase-targeting shRNA serving as negative controls. RNA was collected 72 hours after lentiviral transduction and subjected to RNA sequencing to identify gene-expression changes and molecular pathways associated with C17orf58 depletion.

  扰动筛选
• Attenuation of DOK3 re-programs tumor-associated macrophages to enhance anti-PD-1-mediated cancer immunotherapy
  GSE343606Homo sapiens1 个样本2026-10-26

  Downstream of Kinase 3 (DOK3) is an adaptor protein that binds and modulates Caspase recruitment domain-containing protein 9 (CARD9) signaling but the role for DOK3 during tumor immune escape remains unclear. Here, we revealed immunosuppressive Osteopontin (SPP1+) tumor-associated macrophages (TAMs) to highly express DOK3 while DOK3low/neg TAMs express CARD9 and T cell-homing chemokines within the tumor microenvironment (TME). Interestingly, Dok3-/- mice showed decreased tumor growth and improved response to anti-PD-1 therapy. While DOK3 is constitutively expressed by macrophages, blocking its interaction with CARD9 enhances JNK signaling to reprogram TAMs for improved homing and activation of T cells. Further spatial studies clarified the localization of DOK3high TAMs within the TME and an association of DOK3 expression with progressive disease in an ongoing Phase II study of Lenvatinib/Pembrolizumab in recurrent clear cell gynecological carcinomas. Overall, targeting DOK3-CARD9 axis may represent a new avenue to overcome resistance in cancer immunotherapy by driving the emergence of favorable response-associated TAM states.

  空间转录组
• The antioxidant (+)-Catechin reduces inflammation and promotes a stable plaque phenotype in female LDL receptor deficient mice fed a high-fat diet via anti Inflammatory and smooth muscle cell regulatory pathways [human]
  GSE343575Homo sapiens6 个样本2026-10-26

  Nutraceuticals such as (+)-Catechin are emerging as promising agents for the prevention and treatment of atherosclerotic cardiovascular disease. A large prospective study of 34,492 participants previously demonstrated an inverse association between (+)-Catechin intake and risk for coronary heart disease. Our recent work further showed that (+)-Catechin inhibits several atherosclerosis related processes in vitro, induces beneficial metabolic changes in male C57BL/6J mice fed a high fat diet (HFD), and reduces plaque burden and inflammation in male low-density lipoprotein (LDL) receptor deficient (LDLr / ) mice fed a HFD. Given known sex specific differences in atherosclerosis, it is essential to extend these investigations to female mice. The objective of this study was therefore to investigate the effects of (+)-Catechin in female LDLr / mice in vivo. (+)-Catechin lowered plasma cholesterol levels, reduced circulating T cell populations, and increased several beneficial short chain fatty acids in both the plasma and the faeces. It also decreased plaque size, lipid content, macrophage accumulation, and CD3⁺ T cell infiltration in the aortic root, while enhancing markers of plaque stability. RNA sequencing (RNA seq) of the thoracic aorta revealed modulation of key pathways involved in inflammatory signalling, hypertension and immune responses. Complementary studies in human aortic smooth muscle cells demonstrated that (+)-Catechin attenuated macropinocytosis and oxidised LDL uptake, processes linked to plaque progression, without promoting calcification. RNA seq identified several genes and pathways consistent with the compound’s anti atherogenic and plaque stabilising actions. Collectively, these findings provide new mechanistic insights into the beneficial cardiovascular effects of (+)-Catechin in female mice and support further evaluation of this flavanol in human clinical trials.
• The antioxidant (+)-Catechin reduces inflammation and promotes a stable plaque phenotype in female LDL receptor deficient mice fed a high-fat diet via anti Inflammatory and smooth muscle cell regulatory pathways
  GSE342632Mus musculus6 个样本2026-10-26

  Nutraceuticals such as (+)-Catechin are emerging as promising agents for the prevention and treatment of atherosclerotic cardiovascular disease. A large prospective study of 34,492 participants previously demonstrated an inverse association between (+)-Catechin intake and risk for coronary heart disease. Our recent work further showed that (+)-Catechin inhibits several atherosclerosis related processes in vitro, induces beneficial metabolic changes in male C57BL/6J mice fed a high fat diet (HFD), and reduces plaque burden and inflammation in male low-density lipoprotein (LDL) receptor deficient (LDLr / ) mice fed a HFD. Given known sex specific differences in atherosclerosis, it is essential to extend these investigations to female mice. The objective of this study was therefore to investigate the effects of (+)-Catechin in female LDLr / mice in vivo. (+)-Catechin lowered plasma cholesterol levels, reduced circulating T cell populations, and increased several beneficial short chain fatty acids in both the plasma and the faeces. It also decreased plaque size, lipid content, macrophage accumulation, and CD3⁺ T cell infiltration in the aortic root, while enhancing markers of plaque stability. RNA sequencing (RNA seq) of the thoracic aorta revealed modulation of key pathways involved in inflammatory signalling, hypertension and immune responses. Complementary studies in human aortic smooth muscle cells demonstrated that (+)-Catechin attenuated macropinocytosis and oxidised LDL uptake, processes linked to plaque progression, without promoting calcification. RNA seq identified several genes and pathways consistent with the compound’s anti atherogenic and plaque stabilising actions. Collectively, these findings provide new mechanistic insights into the beneficial cardiovascular effects of (+)-Catechin in female mice and support further evaluation of this flavanol in human clinical trials.
• Attenuation of DOK3 re-programs tumor-associated macrophages to enhance anti-PD-1-mediated cancer immunotherapy [scRNA-seq MC38]
  GSE341712Mus musculus12 个样本2026-10-26

  Downstream of Kinase 3 (DOK3) is an adaptor protein that binds and modulates Caspase recruitment domain-containing protein 9 (CARD9) signaling but the role for DOK3 during tumor immune escape remains unclear. Here, we revealed immunosuppressive Osteopontin (SPP1+) tumor-associated macrophages (TAMs) to highly express DOK3 while DOK3low/neg TAMs express CARD9 and T cell-homing chemokines within the tumor microenvironment (TME). Interestingly, Dok3-/- mice showed decreased tumor growth and improved response to anti-PD-1 therapy. While DOK3 is constitutively expressed by macrophages, blocking its interaction with CARD9 enhances JNK signaling to reprogram TAMs for improved homing and activation of T cells. Further spatial studies clarified the localization of DOK3high TAMs within the TME and an association of DOK3 expression with progressive disease in an ongoing Phase II study of Lenvatinib/Pembrolizumab in recurrent clear cell gynecological carcinomas. Overall, targeting DOK3-CARD9 axis may represent a new avenue to overcome resistance in cancer immunotherapy by driving the emergence of favorable response-associated TAM states.

  单细胞空间转录组
• T cell Mechanomemory Takes Training
  GSE341175Homo sapiens8 个样本2026-10-26

  Biomaterials provide a powerful tool for directing the function of T cells, mediators of adaptive immunity and cellular immunotherapy. As an intriguing facet of biomaterial design, modulating the mechanical stiffness of biomaterials provides control over T cell activation, optimizing expansion through a parameter that is orthogonal to and can be combined with other approaches. A key question is whether mechanosensing is limited to immediate impacts on cell function or includes long-lasting imprints on cell function. This report demonstrates such a mechanomemory in the context of expansion of T cells for immunotherapy; populations activated on mechanically soft surfaces exhibit an extended proliferative phase for multiple generations following removal from the substrate. Using media manipulation, this report shows that mechanomemory is mediated by both intrinsic, epigenetic changes and extrinsic factors associated with cell-cell signaling. Moreover, the impact of extrinsic factors decreases over the course of expansion. The development and solidification of mechanomemory in T cells over multiple cell divisions provides new design rules for optimization and insights into how these agents interpret mechanically complex microenvironments.
• Attenuation of DOK3 re-programs tumor-associated macrophages to enhance anti-PD-1-mediated cancer immunotherapy [scRNA-seq]
  GSE341136Homo sapiens6 个样本2026-10-26

  Downstream of Kinase 3 (DOK3) is an adaptor protein that binds and modulates Caspase recruitment domain-containing protein 9 (CARD9) signaling but the role for DOK3 during tumor immune escape remains unclear. Here, we revealed immunosuppressive Osteopontin (SPP1+) tumor-associated macrophages (TAMs) to highly express DOK3 while DOK3low/neg TAMs express CARD9 and T cell-homing chemokines within the tumor microenvironment (TME). Interestingly, Dok3-/- mice showed decreased tumor growth and improved response to anti-PD-1 therapy. While DOK3 is constitutively expressed by macrophages, blocking its interaction with CARD9 enhances JNK signaling to reprogram TAMs for improved homing and activation of T cells. Further spatial studies clarified the localization of DOK3high TAMs within the TME and an association of DOK3 expression with progressive disease in an ongoing Phase II study of Lenvatinib/Pembrolizumab in recurrent clear cell gynecological carcinomas. Overall, targeting DOK3-CARD9 axis may represent a new avenue to overcome resistance in cancer immunotherapy by driving the emergence of favorable response-associated TAM states.

  单细胞空间转录组
• Single-cell RNA sequencing of visceral adipose tissue CD45+ immune cells from saline- and recombinant ANXA8 (rANXA8)-treated diet-induced obese mice
  GSE341132Mus musculus2 个样本2026-10-26

  Visceral obesity drives adipose tissue macrophage (ATM) inflammation. To resolve adipose immune-cell heterogeneity beyond the M1/M2 framework and define how the visceral adipose-derived adipokine Annexin A8 (ANXA8) remodels the immune landscape, we performed droplet-based single-cell RNA sequencing (MobiCube 3' RNA) of CD45+ immune cells isolated from the stromal vascular fraction (SVF) of visceral (gonadal) adipose tissue of diet-induced obese male C57BL/6 mice treated with either saline (vehicle) or recombinant ANXA8 protein (rANXA8, 2.5 mg/kg/day, i.p., 4 weeks). Unbiased clustering resolved multiple macrophage subpopulations (perivascular [PVM], lipid-associated [LAM] and nerve-associated [NAM] macrophages) alongside monocytes, dendritic cells and other immune and stromal cells. rANXA8 treatment reduced pro-inflammatory and increased anti-inflammatory/homeostatic transcriptional programs across macrophage subpopulations, indicating that ANXA8 reprograms the adipose macrophage landscape toward a less inflammatory, more homeostatic state.

  单细胞
• Hyperglycemia drives an activated, lipid-laden non-classical monocyte phenotype in diabetes
  GSE339503Mus musculus36 个样本2026-10-26

  The presence of lipid-loaded macrophages in the artery wall and kidney characterizes diabetic atherosclerotic cardiovascular disease and diabetic kidney disease, respectively. Monocytes, the bone marrow-derived precursors of macrophages, accumulate lipids in response to hypercholesterolemia; however, whether diabetes directly alters monocyte lipid loading remains unclear. Using unbiased proteomics, we show that diabetes profoundly affects circulating monocytes, leading to upregulation of glucose metabolism pathways and suppression of cholesterol homeostasis pathways, indicative of lipid loading, particularly in non-classical monocytes. Functional analyses confirmed that non-classical monocytes exhibit increased glucose uptake and a lipid-loaded phenotype in three distinct mouse models of diabetes, and that they are also more lipid-loaded in people living with diabetes. The increased lipid loading of non-classical monocytes was not only due to dyslipidemia but to elevated glucose levels. Finally, we find that non-classical monocytes traffic to the kidney and contribute to a foamy population of kidney macrophages in a mouse model of diabetes. Together, these findings suggest that hyperglycemia in diabetes drives the reprogramming of non-classical monocytes, leading to lipid loading and the accumulation of lipid-loaded macrophages in the kidney.
• Effect of TNFR2 agonism on human regulatory T cells
  GSE339300Homo sapiens10 个样本2026-10-26

  We isolated CD45RA+ Treg cells from human peripheral blood and treated them in vitro using a human TNFR2 agonist or a control VHH.
• Attenuation of DOK3 re-programs tumor-associated macrophages to enhance anti-PD-1-mediated cancer immunotherapy
  GSE338696Homo sapiens408 个样本2026-10-26

  Downstream of Kinase 3 (DOK3) is an adaptor protein that binds and modulates Caspase recruitment domain-containing protein 9 (CARD9) signaling but the role for DOK3 during tumor immune escape remains unclear. Here, we revealed immunosuppressive Osteopontin (SPP1+) tumor-associated macrophages (TAMs) to highly express DOK3 while DOK3low/neg TAMs express CARD9 and T cell-homing chemokines within the tumor microenvironment (TME). Interestingly, Dok3-/- mice showed decreased tumor growth and improved response to anti-PD-1 therapy. While DOK3 is constitutively expressed by macrophages, blocking its interaction with CARD9 enhances JNK signaling to reprogram TAMs for improved homing and activation of T cells. Further spatial studies clarified the localization of DOK3high TAMs within the TME and an association of DOK3 expression with progressive disease in an ongoing Phase II study of Lenvatinib/Pembrolizumab in recurrent clear cell gynecological carcinomas. Overall, targeting DOK3-CARD9 axis may represent a new avenue to overcome resistance in cancer immunotherapy by driving the emergence of favorable response-associated TAM states.

  空间转录组
• Non-enzymatic functions of CBP/EP300 are harnessed by gene-targeted inducers of proximity [RNA-seq]
  GSE337925Homo sapiens8 个样本2026-10-26

  Friedreich’s ataxia (FRDA) is a rare neurodegenerative disease caused by an expansion of GAA-trinucleotide repeats within the frataxin (FXN) gene. These GAA repeat expansions are enriched in repressive chromatin marks that accompany near complete silencing of the gene. Restoring FXN expression is thus a curative therapeutic goal. Here, we report the development of bifunctional synthetic gene regulators (SynGR-KATs) that recruit lysine acetyl transferases CBP/KAT3A and EP300/KAT3B to GAA repeat expansions. The GAA-targeted enzymes install transcriptionally conducive acetyl marks on proximal chromatin and restore FXN expression. Proximity-induced pharmacology of CBP/EP300 focuses solely on the enzymatic activity of these multi-domain proteins; however, we find that the non-enzymatic protein scaffolding functions contribute in equal measure to FXN expression. Highlighting the importance of protein scaffolding, co-treatment of patient-derived FRDA cells with BRD4/BET-binding SynGRs (SynGR-BETs) along with SynGR-KATs enhanced FXN expression beyond what can be achieved by either class of molecules on their own. Thus, SynGR-KATs serve as invaluable probes of transcriptional regulation while also providing a new path to therapeutic restoration of FXN expression.
• Mechanisms of risk in pregnancy-associated triple negative breast cancer: insights from spatial omics [2]
  GSE335330Homo sapiens917 个样本2026-10-26

  Pregnancy-associated triple-negative breast cancer (PA-TNBC) is a highly aggressive, hard-to-treat malignancy, with increased risk linked to post-lactational mammary gland involution. To understand this, we used GeoMx Digital Spatial Profiler to analyze the transcriptional landscape of 46 treatment-naïve PA-TNBC tissues from 33 women (10 pre-involution/PRE; 23 post-involution/POST, diagnosed within 3 years of delivery), focusing on epithelial and microenvironmental changes. Our findings reveal that the most significant transcriptional differences between PRE and POST exist in non-invasive epithelia and during the transition to invasion. POST non-invasive epithelia showed distinct activation of inflammatory and developmental pathways, while transitioning to TNBC involved elevated chromatin remodeling and migration. Notably, the tumor microenvironment (TME) surrounding POST invasive epithelia featured the greatest immune cell infiltration yet also increased immune exhaustion. Pseudotime analysis highlighted the 1–2 year postpartum window as having the strongest inflammatory signaling. These results underline the need for early molecular detection in normal-appearing post-involution tissues and suggest that targeting the TME is a viable strategy for treating POST PA-TNBC.

  空间转录组
• Mechanisms of risk in pregnancy-associated triple negative breast cancer: insights from spatial omics [1]
  GSE335314synthetic construct; Homo sapiens921 个样本2026-10-26

  Pregnancy-associated triple-negative breast cancer (PA-TNBC) is a highly aggressive, hard-to-treat malignancy, with increased risk linked to post-lactational mammary gland involution. To understand this, we used GeoMx Digital Spatial Profiler to analyze the transcriptional landscape of 46 treatment-naïve PA-TNBC tissues from 33 women (10 pre-involution/PRE; 23 post-involution/POST, diagnosed within 3 years of delivery), focusing on epithelial and microenvironmental changes. Our findings reveal that the most significant transcriptional differences between PRE and POST exist in non-invasive epithelia and during the transition to invasion. POST non-invasive epithelia showed distinct activation of inflammatory and developmental pathways, while transitioning to TNBC involved elevated chromatin remodeling and migration. Notably, the tumor microenvironment (TME) surrounding POST invasive epithelia featured the greatest immune cell infiltration yet also increased immune exhaustion. Pseudotime analysis highlighted the 1–2 year postpartum window as having the strongest inflammatory signaling. These results underline the need for early molecular detection in normal-appearing post-involution tissues and suggest that targeting the TME is a viable strategy for treating POST PA-TNBC.

  空间转录组
• Oxidative Stress Potentiates a STAT1–APOL1 Feedforward Loop and Governs Disease Severity in APOL1-Mediated Kidney Disease [Xenium]
  GSE334605Mus musculus2 个样本2026-10-26

  Introduction: Apolipoprotein L1 (APOL1) risk variants (G1 and G2) confer immunity against Trypanosoma infection but markedly increase susceptibility to progressive kidney disease. However, only a subset of biallelic risk-variant carriers develops disease progression, distinct from murine models. Here, we evaluated molecular drivers of progressive disease using a model that reflected the low human disease penetrance. Methods: To investigate the heterogeneity of APOL1-mediated kidney disease, we generated novel APOL1 bacterial artificial chromosome transgenic mice with doxycycline-inducible systemic IFNγ expression (G0- or G1-IFNγ mice). Single-cell spatial transcriptomics via 10x Genomics Xenium In Situ platform was performed.

  单细胞空间转录组
• Endonucleolytic mRNA decay associated with damaged tRNAs occupying the ribosome
  GSE334514Saccharomyces cerevisiae45 个样本2026-10-26

  Aberrant events during mRNA translation trigger ribosome-dependent quality control mechanisms that tune mRNA decay and gene expression. Here, we describe endonucleolytic mRNA decay associated with damaged tRNAs at the ribosome. We provide evidence that this process is associated with a nicked tRNA that our data place in the ribosomal A-site, where it contributes to ribosome stalling. Genetic analyses suggest that the pathway is independent of canonical mRNA decay machinery, and we identify the CTDK-I complex as a critical regulator. These findings suggest that the ribosomal A-site can engage damaged tRNAs and that this engagement can trigger mRNA decay, broadening our understanding of translation elongation and tRNA biology.
• Preconception Paternal PFAS Exposure Reprograms the Placental Epigenome
  GSE333805Mus musculus28 个样本2026-10-26

  The placenta plays a vital role in supporting fetal growth and development by facilitating nutrient exchange, hormone signalling and immune regulation. Environmental toxicants such as perfluoroalkyl and polyfluoroalkyl substances (PFAS) can disrupt placental homeostasis, leading to increased risk of disease later in life. Paternal environmental exposures may influence offspring health by inducing epigenetic changes in sperm, which may affect sex-dependent placental programming. Here, male mice were exposed to a PFAS mixture (PFOS, PFOA, PFNA, PFHxS, GenX; 20 μg/L each) for 10 weeks and mated with unexposed females. We identified 6,656 and 3,242 differentially methylated regions (DMRs) in E12.5 placentas of female and male offspring, respectively. Female placentas showed predominantly hypermethylation (78.5%), whereas male placentas were mostly hypomethylated (62%). Gene ontology analyses linked female placental DMRs to cell and embryonic morphogenesis, and male DMRs to anatomical size regulation and hemostasis. Bulk RNA sequencing revealed 168 and 148 differentially expressed genes (DEGs) in female and male placentas, respectively. Female DEGs were related to immune regulation, while male DEGs were involved in muscle and mesenchyme development. Sex-by-PFAS interaction models identified distinct methylation and transcription biological pathways. Overlap analysis between F0 sperm and F1 placentas identified 265 shared genes, including 289 female-specific and 124 male-specific genes. Paternal exposure to the PFAS mixture increased glycogen concentrations in male, but not female, placentas. No effects were observed at imprinted loci. These findings demonstrate that paternal preconception exposure to a PFAS mixture alter placental epigenomic and transcriptomic landscapes, which may contribute to sex-dependent trajectories of fetal health and development and offspring phenotypes.
• The nail mesenchyme creates a regeneration-specific ligand environment that orchestrates mammalian regeneration versus fibrotic wound healing [scRNA-seq]
  GSE326786Mus musculus4 个样本2026-10-26

  The adult digit tip is one of the few privileged mammalian tissues that can regenerate. Here, we have asked why this is so. We show, using single cell spatial transcriptomics and genetic mouse models that regeneration requires the nail organ and associated inductive nail mesenchyme, and that in their absence the digit tip undergoes fibrotic wound-healing. We further show the nail organ/mesenchyme orchestrates a highly-organized regenerative response where mesenchymal cells are reprogrammed to a blastema state and re-epithelialization is enhanced. It does this by creating a regeneration-specific ligand environment that is absent in the nonregenerative condition and that includes multiple BMPs. Loss of downstream BMP signaling by genetic deletion of Smad4 in all mesenchymal cells or specifically in the nail mesenchyme inhibits multiple aspects of the regenerative response, including expression of regeneration-specific ligands. Thus, the nail mesenchyme creates a BMP-rich local ligand environment that reprograms mesenchymal cells to a blastema state and promotes tissue regeneration versus fibrotic wound-healing, findings with implications for tissue repair and anti-fibrosis strategies.

  单细胞空间转录组
• The nail mesenchyme creates a regeneration-specific ligand environment that orchestrates mammalian regeneration versus fibrotic wound healing
  GSE326776Mus musculus98 个样本2026-10-26

  The adult digit tip is one of the few privileged mammalian tissues that can regenerate. Here, we have asked why this is so. We show, using single cell spatial transcriptomics and genetic mouse models that regeneration requires the nail organ and associated inductive nail mesenchyme, and that in their absence the digit tip undergoes fibrotic wound-healing. We further show the nail organ/mesenchyme orchestrates a highly-organized regenerative response where mesenchymal cells are reprogrammed to a blastema state and re-epithelialization is enhanced. It does this by creating a regeneration-specific ligand environment that is absent in the nonregenerative condition and that includes multiple BMPs. Loss of downstream BMP signaling by genetic deletion of Smad4 in all mesenchymal cells or specifically in the nail mesenchyme inhibits multiple aspects of the regenerative response, including expression of regeneration-specific ligands. Thus, the nail mesenchyme creates a BMP-rich local ligand environment that reprograms mesenchymal cells to a blastema state and promotes tissue regeneration versus fibrotic wound-healing, findings with implications for tissue repair and anti-fibrosis strategies.

  单细胞空间转录组
• RNA Polymerase II Dynamics in Antiviral NK Cell Responses [Histone ChIP-Seq]
  GSE326752Mus musculus26 个样本2026-10-26

  Natural killer (NK) cells are innate lymphocytes that uniquely exhibit both innate and adaptive responses towards certain pathogens. During cytomegalovirus (CMV) infection, antigen-specific NK cells will generate a long-lived pool of memory cells with enhanced responses to secondary infection. The underlying molecular mechanisms that regulate early innate effector functions and delayed adaptive proliferation followed by longevity during antiviral NK cell differentiation remain to be fully understood. Here, we investigated the dynamics of serine-5 phosphorylated RNA Polymerase II (Pol IIS5P) occupancy in NK cells ex vivo during mouse CMV (MCMV) infection. During the initial NK cell antiviral response, Pol IIS5P occupancy increased broadly across the genome, at both upregulated and downregulated genes relative to NK cells at rest. NK cells across response states showed distinct enrichment of Pol IIS5P at transcriptional start sites (TSS) versus non-promoter regions with select genes maintaining Pol IIS5P occupancy throughout MCMV infection to the memory phase. Thus, our findings illustrate the dynamic Pol IIS5P genomic occupancy in NK cells during antiviral immunity.
• MEK2 Suppresses IL-4 Polarization via PPARγ and Negatively Impacts Macrophage Epithelial Crosstalk to Delay Repair
  GSE326260Mus musculus12 个样本2026-10-26

  In this study, we tested our hypothesis that MEK2 impairs IL-4 (reparative) macrophage function. Transcriptional profiling of WT and Mek2-/- bone marrow derived macrophages (BMDM) revealed that MEK2 inhibits a subset of IL-4-dependent gene expression, including genes enriched in wound repair pathways.