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。

• Single-cell RNA sequencing of appendiceal adenocarcinoma reveals a low proportion of epithelial cells and a fibroblast enriched tumor microenvironment
  GSE352702Homo sapiens4 个样本2026-10-31

  Appendiceal adenocarcinoma (AA) is an understudied gastrointestinal malignancy. Treatment is guided by its proximal counterpart, colorectal cancer (CRC), despite recent studies demonstrating AA’s unique mutational landscape and poor response to CRC chemotherapy. As the first application of single-cell technology to AA these data provide insight into the intratumor heterogeneity of AA and highlight the important contribution of the tumor microenvironment in this orphan disease. These results also reinforce multiple observations that AA is a unique disease entity from CRC and targeting the tumor microenvironment should be considered as a therapeutic strategy.

  单细胞
• Local chromatin, 3D genome folding and transposon cargo shape Sleeping Beauty transposition
  GSE352692Mus musculus489 个样本2026-10-31

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Longitudinal spatial mapping of tumor–immune microenvironment following electrochemotherapy of cutaneous melanoma metastases
  GSE352662Homo sapiens16 个样本2026-10-31

  Background: Electrochemotherapy (ECT) utilizes reversible electroporation for localized chemotherapeutic delivery, where beyond local cytotoxicity, ECT acts as an in situ immunomodulator. However, the dynamic spatial orchestration of the TME that translates this localized therapy into potential abscopal-like responses in untreated lesions remains poorly understood. Methods: To uncover the mechanisms of evolving tumor microenvironment (TME) that dictate this immune activation, we applied Xenium spatial transcriptomics to longitudinally sampled in-transit cutaneous melanoma metastases from three patients, capturing baseline immune states and two distinct post-ECT intervals (two-to-three and nine-to-ten days). Furthermore, to explicitly characterize potential abscopal-like effects, biopsies were collected also from non-treated lesions. Following sample integration, we annotated cell types and identified functional subpopulations of key compartments, which we compared across treatment timepoints and patients. Further, we resolved functional spatial niches and identified spatially localized immune front, which we characterized and linked to patients' clinical responses. Results: Our analysis uncovered heterogeneous patient trajectories: a robust local and regional responder, a localized-only responder, and a delayed regional responder. These divergent outcomes were linked to baseline TME heterogeneity that was reflected by diverging proportions of functional spatial niches. While the partial responder exhibited an immune-cold architecture, complete responders were characterized by an immune-permissive TME with a prominent immune front at the interface of malignant and immune-active niches. Molecular profiling of these spatial boundaries exposed patient-specific signatures of activation and suppression within infiltrating T cells, myeloid cells, and fibroblasts. Although the states of malignant cells remained predominantly unchanged in the partial responder, the malignant cells of complete responders transitioned into a unique SOX2-OT-expressing dormant state, sequestered within keratinocyte-rich zones and characterized by an immunosuppressive signature post-treatment. Conclusions: Together, our findings suggest that beside local ablation, ECT might actively instigate regional antitumor immunity, a therapeutic effect that we observed in two patients harboring a permissive TME. Further, our deep spatial TME profiling identifies several exploratory observations on the effects of ECT that should be addressed in future studies.

  空间转录组
• Local and circulating cytotoxic CD4 T cells are early markers of disease activity in pediatric Crohn’s disease
  GSE352630Homo sapiens8 个样本2026-10-31

  Inflammatory bowel disease (IBD) requires improved molecular and cellular stratification to guide therapy. In the PREDICT study, we profiled intestinal and blood T cells from treatment-naïve pediatric patients with IBD, disorders of gut–brain interaction controls, and healthy donors using single-cell RNA sequencing. Across 107 participants, we identify a population of clonally expanded cytotoxic CD4 T cells (CD4 CTL) enriched in the inflamed gut of patients with Crohn's disease (CD) and ulcerative colitis. Cell–cell interaction analyses and validation in a mouse model implicate IL-27 in CD4 CTL differentiation. Elevated CD4 CTL frequencies in gut and peripheral blood at diagnosis are associated with subsequent poor outcome of anti-TNF therapy in pediatric CD. Findings in our identification cohort are validated in an independent cohort and through reanalysis of published datasets. Blood CD4⁺CXCR6⁺CD27⁻ T cells displayed a CD4 CTL transcriptional phenotype, supporting CD4 CTLs as a candidate blood-accessible biomarker for treatment stratification.

  单细胞
• Cooperative interaction of Foxp3 and STAT5 confers regulatory T cell fitness by tuning IL-2-induced gene expression [ATAC-Seq]
  GSE352613Mus musculus32 个样本2026-10-31

  Transcription factor Foxp3, with its singular role in differentiation and function of regulatory T (Treg) cells in physiologic and inflammatory settings, is thought to act by modulating transcriptional responses to activatory extracellular cues including pro-inflammatory cytokines. However, the underlying mechanisms remain largely unknown. After Foxp3 is induced during Treg differentiation upon STAT5 activation downstream of interleukin-2 receptor (IL-2R), sustained STAT5 signaling facilitates fitness and suppressive capacity of mature Treg cells. We found that Foxp3 and phospho-STAT5 (pSTAT5) form a stable transcriptional complex. Upon IL-2 sensing, Foxp3 is recruited in a pSTAT5-dependent manner to GAS-motif-enriched cis-regulatory elements that are developmentally primed by STAT5 in Treg precursors prior to Foxp3 expression. Using chemogenetically and pharmacologically induced protein degradation, we demonstrate that Foxp3 modulates STAT5 signaling in activated Treg cells to selectively modulate their transcriptional response to IL-2, most prominently involving a Myc-dependent gene module. Our studies suggest that direct Foxp3-STAT5 cooperativity fine-tunes STAT5 signaling downstream of IL-2 receptor activation to support functionality of differentiated Treg cells.
• Transcriptomic profiling of Gem-miR-15a treatment in parental and drug resistant HCT116 colorectal cancer cells
  GSE352606Homo sapiens4 个样本2026-10-31

  Resistance to 5-fluorouracil (5-FU)-based chemotherapy is a major obstacle in colorectal cancer (CRC). Gem-miR-15a, a gemcitabine-modified tumor-suppressor microRNA-15a mimic, was developed to overcome chemoresistance by combining the tumor-suppressive activity of miR-15a with the cytotoxic activity of gemcitabine in a single, vehicle-free molecule. To investigate the transcriptomic basis of its activity and its ability to reverse resistance-associated gene expression, RNA-sequencing was performed on parental and 5-FU-resistant HCT116 CRC cells under untreated and Gem-miR-15a-treated conditions. Analysis of these profiles identified modulation of key oncogenic and stress-response pathways and reversal of resistance-associated expression patterns following Gem-miR-15a treatment.
• Cooperative interaction of Foxp3 and STAT5 confers regulatory T cell fitness by tuning IL-2-induced gene expression [Myc_RNA]
  GSE352602Mus musculus6 个样本2026-10-31

  The transcription factor Foxp3, with its singular role in the differentiation and function of regulatory T (Treg) cells, is thought to modulate their responses to activatory extracellular cues. However, the underlying mechanisms remain largely unknown. Beyond its requirement for Foxp3 induction during Treg differentiation, STAT5 activation downstream of interleukin-2 (IL-2) signaling is essential for the fitness, activation, and suppressive capacity of mature Treg cells. Here, we demonstrate that IL-2-induced phospho-STAT5 directly binds Foxp3, endowing Foxp3 with a new binding specificity and enabling its recruitment to a distinct set of GAS motif-enriched cis-regulatory elements. Using acute chemogenetic and pharmacological protein degradation strategies, we show that Foxp3 selectively modulates STAT5-dependent transcriptional responses of activated Treg cells to IL-2, including a Myc-dependent gene module. These results suggest that Foxp3-STAT5 complexes “customize” transcriptional responses of activated Treg cells to IL-2 stimulation to support their fitness and functionality.
• Integrated transcriptomic and tissue profiling reveals imprinted-gene dysregulation and PEG10 upregulation in liposarcoma
  GSE352573Homo sapiens42 个样本2026-10-31

  Liposarcoma is a rare cancer, comprising four major histological subtypes with distinct molecular features and limited therapeutic options in advanced disease. We investigated subtype-associated transcriptional programmes, imprinted-gene dysregulation and the expression context of PEG10 in liposarcoma. Bulk RNA sequencing was performed on 16 independent liposarcoma tumours and five adjacent non-tumour tissues. PEG10 was further examined by RT-qPCR, RNA fluorescence in situ hybridisation (RNA-FISH), exploratory TCGA-SARC survival analysis and an external single-cell RNA-sequencing dataset of dedifferentiated liposarcoma. Transcriptomic profiling identified subtype-associated programmes and significant enrichment of imprinted genes in liposarcoma. PEG10 showed tumour-associated upregulation supported by RT-qPCR and RNA-FISH. PEG10 was detectable across all major subtypes, with the highest bulk transcript levels in myxoid liposarcoma, while RNA-FISH signal was higher in G3 than G2 tumours. In TCGA-SARC, higher PEG10 expression was associated with shorter overall survival, whereas DDLPS-specific analyses were not significant. External single-cell data localised PEG10 predominantly to tumour and cycling-cell populations and to angiogenesis- and invasion-associated tumour-cell states. Histological subtype accounted for a substantial component of PEG10-associated pathway variation. These findings identify PEG10 as a tumour-associated imprinted transcript in liposarcoma and provide a framework for further investigation of its biological and clinical relevance in larger, subtype-balanced cohorts.

  单细胞
• Circulating microRNA profiles in patients with MASLD-related cirrhosis and hepatic encephalopathy: an exploratory pilot study
  GSE352557Homo sapiens14 个样本2026-10-31

  Background and Aims: Hepatic encephalopathy (HE) is a common complication of cirrhosis, characterized by biochemical alterations in the central nervous system microenvironment. Although the molecular mechanisms underlying HE have been partly characterized at the protein level, their upstream regulation remains poorly understood. This study aimed to characterize circulating microRNA (miRNA) expression in patients with overt HE and identify the biological pathways associated. Materials and methods: Ten patients with MASLD-related cirrhosis and HE and four controls – subjects without chronic liver disease – attending the Liver Unit of the University Hospital of Messina, were enrolled after the exclusion of neurological comorbidities. Blood samples were collected at enrolment, cell-free RNA was isolated from plasma using the miRNeasy Kit, and functional enrichment analysis was performed using DIANA-miRPath v4. Results: Compared with controls, patients with HE showed downregulation of miR-18a and upregulation of miR-150, miR-214, miR-296, miR-320, miR-423-5p, miR-483-5p, miR-484, miR-486, miR-636, miR-92a, miR-10b, miR-1233, miR-1255b, miR-1285, miR-1290, miR-1291, miR-30a-5p, miR-338-5p, and miR-378. Functional enrichment analysis identified pathways and molecular functions related to glycolipid metabolism regulators and neuronal homeostasis signalling. Conclusion: Study results reveal a complex miRNA-associated network involving metabolic dysfunction, neuroinflammation, cellular integrity, and neuronal plasticity, highlighting the biological complexity of MASLD-related cirrhosis with HE. Keywords: Metabolic dysfunction-associated steatotic liver disease, liver cirrhosis, hepatic encephalopathy, microRNAs.
• The CRISPR-Cas system functions as a regulatory module in Salmonella enterica serovar Typhi
  GSE352555Salmonella enterica subsp. enterica serovar Typhi str. CT18; Salmonella enterica subsp. enterica serovar Typhi; Salmonella enterica subsp. enterica serovar Typhimurium str. LT27 个样本2026-10-31

  Transcriptional profile of Salmonella enterica serovar Typhi IMSS-1 mutants lacking individual components of the Type I-E CRISPR-Cas system. Strains carrying deletions of cas1, cas2, cas3, casB (cse2), casD (cas5), casE (cas6e) or the cas3-CRISPR region were compared with the wild-type strain, which was used as control. All strains were grown in N-minimal medium at 37 °C to an OD600 of 0.6. CRISPR-Cas systems are best known as adaptive immune systems of bacteria against phages and plasmids, but they are increasingly recognized as regulators of endogenous gene expression. The aim of the experiment was to learn if the loss of CRISPR-Cas components was able to modify the overall mRNA expression profile of S. Typhi. Here, we demonstrate that the Type I-E CRISPR-Cas system in S. Typhi modulates the expression of the key transcriptional regulator TviA.
• Analysis of Sacituzumab Govitecan-Resistant Syngeneic Patient-Derived Xenograft Pairs
  GSE352548Homo sapiens18 个样本2026-10-31

  This study identifies RNA expression changes in models that have acquired Sacituzumab Govitecan (SG) resistance over extended treatment in triple-negative breast cancer patient-derived xenograft (PDX) models. Patients diagnosed with triple-negative breast cancer do not have many targeted treatment options, yet SG has recently been approved for first-line treatment of these patients. SG is an antibody drug conjugate that binds to TROP2 and delivers a topoisomerase 1 inhibitor, SN-38, as its payload. We have selected three PDX models which were initially sensitive to SG treatment, and treated them with suboptimal doses of SG until the tumors grew through treatment. Previous studies have shown that resistance to SG could be due to inefficient antibody internalization or lack of payload efficacy, however, other genetic or transcriptomic factors may influence drug sensitivity. We hypothesize that individual acquired SG resistance mechanisms will uncover features that can be targeted to extend the duration of response to SG.
• Gut microbial equol production associates with cognitive trajectories and suppresses NLRP3 inflammasome activation
  GSE352509Mus musculus12 个样本2026-10-31

  Many intestinal microbiome-produced metabolites have neuroimmunomodulatory properties. To identify metabolites associated with cognition and neuroinflammation, we measured microbially derived metabolites in the blood serum of 1,206 cognitively normal participants from the Wisconsin Alzheimer’s Disease Research Center (ADRC) and the Wisconsin Registry for Alzheimer’s Prevention (WRAP). We found that serum presence of equol, a microbially-produced metabolite derived from the soy-isoflavone daidzein, was related to preclinical cognition over time in a sex-dependent manner, suggesting that microbe-derived equol may attenuate cognitive decline through sex-specific biological pathways. Additionally, serum equol was associated with slower accumulation of the CSF biomarkers GFAP, S100B, and NfL, suggesting equol may be linked to glial regulation and neuronal integrity. To understand how equol may mediate inflammation systemically to reduce neuroinflammation, we performed bulk RNA-sequencing on bone marrow-derived macrophages (BMDMs) and found S-equol treatment modestly altered pathways associated with the NOD, LRR, and pyrin domain containing (NLRP3) inflammasome, an established driver of neuroinflammation in Alzheimer’s disease. We used ELISAs and caspase-1 immunoblots to show S-equol inhibits NLRP3 activation in BMDMs, evidenced by significantly decreased IL-1β secretion and caspase-1 processing after equol treatment. We confirmed that this effect is directly dependent on equol’s inhibition of potassium efflux. These findings lay a strong foundation for future studies examining the neuroimmunomodulatory action of equol in NLRP3 driven disease and cognitive decline.
• Targeting the Alk4 pathway protects against age-related bone loss.
  GSE352343Mus musculus15 个样本2026-10-31

  Osteoporosis is a chronic age-related condition where imbalanced activities between bone-forming osteoblasts and bone-resorbing osteoclasts result in the progressive loss of bone volume and reduced bone quality. While drugs that target osteoclast activity have been developed, there remains a lack of efficient therapies that increase osteoblast function in aging bones. Here, we showed that in mouse femurs, levels of Activin signaling progressively increased with age and strongly correlated with the loss of trabecular bone. When we removed Alk4, the type I receptor for Activin in osteoblast progenitors, Alk4 cKO mice had increased numbers of osteoblasts, an increased rate of bone formation, and increased trabecular bone acquisition. These results indicate that Activin through Alk4 signaling inhibits bone formation and osteoblast activity and is likely associated with osteoporosis. Furthermore, when we injected 2-year-old male mice with Alk4-Fc to capture circulating Activin, aged mice were protected against loss of trabecular bone in both femurs and L5 vertebrae. Remarkably, Alk4-Fc also prevented the age-related decrease in muscle mass that normally accompanies age-related bone loss, indicating that circulating Activins also play a role in sarcopenia. In summary, our preclinical mouse models reveal that circulating Activins play a primary role in age-related bone and muscle loss and can be efficiently targeted to alleviate osteoporosis and sarcopenia in aging mice.
• Baseline immune transcriptional states predict future HIV-1 acquisition in individuals at risk of sexual infection
  GSE352331Homo sapiens104 个样本2026-10-31

  Natural resistance to HIV-1 acquisition in highly exposed seronegative (HESN) individuals suggests the existence of pre-existing host states associated with reduced susceptibility. However, the baseline molecular determinants of susceptibility remain poorly understood. We analyzed PBMC transcriptomes by RNA sequencing in 104 HIV-1-seronegative men who have sex with men (MSM) at high risk of sexual exposure, including 65 HESN and 39 who subsequently seroconverted. Differential expression, functional enrichment, and spatial genomic clustering analyses were integrated with Elastic Net regularized logistic regression. HESN individuals showed enrichment of sensory receptor (p.adj=2×10⁻¹⁶) and cell-adhesion pathways (p.adj=9×10⁻³), together with non-random genomic clustering (p.adj=1×10⁻⁴) of differentially expressed genes at immune-related loci, including TCR, IGH, KIR, and MHC/HLA regions. In contrast, future seroconverters exhibited increased mRNA metabolism (p.adj=1.5×10⁻¹⁴), immune activation (p.adj=0.01), and type I interferon signaling (p.adj=0.02). A 14-gene risk score showed an out-of-fold AUC of 0.888. Cross-cohort transportability was evaluated in an independent ectocervical RNA-seq dataset. Applied without refitting, the signature showed moderate discrimination between long-term HESN and HIV-negative women at high risk of acquisition (AUC=0.689). The out-of-fold molecular risk score was also associated with time to HIV-1 seroconversion in MSM (log-rank p=7.1×10⁻¹¹; score×time interaction p=0.0086). These findings identify distinct pre-infection transcriptional states associated with HIV-1 acquisition and support partially transportable transcriptional architecture across blood and genital mucosal compartments.

  空间转录组
• Local chromatin, 3D genome folding and transposon cargo shape Sleeping Beauty transposition [tagmap]
  GSE352288Mus musculus481 个样本2026-10-31

  The cut-and-paste DNA transposon Sleeping Beauty (SB) is widely used for genome engineering, mutagenesis and gene delivery. When mobilized from a genomic donor position (“launch site”), SB preferentially reintegrates locally (< 2 Mb), but factors governing its transposition from genomic sites remain incompletely understood. Here we analysed local transposition experiments in mouse embryonic stem cells to determine the influence of chromatin context and transposon cargo on SB transposition. Transposons in launch sites with transcriptionally active, accessible chromatin showed lower transposition efficiency. Large cargo and cargo with higher transcriptional activity also result in reduced transposition efficiency. After excision, local reintegration patterns closely resembled 3D contact frequencies of the launch site. This indicates that chromosome folding is a major determinant of the transposition pattern. Surprisingly, we did not detect any effect of the destination chromatin composition on reintegration efficiency. Cargo sequence modified the reintegration patterns: promoter-containing cargo increased both very proximal (<10kb) and interchromosomal transpositions, while CTCF binding sites in the cargo increased reintegration on the launch chromosome. Together, these results define key determinants of SB transposition in chromosomes and inform the design of SB-based genome engineering strategies.
• Local chromatin, 3D genome folding and transposon cargo shape Sleeping Beauty transposition [pADam]
  GSE352286Mus musculus8 个样本2026-10-31

  The cut-and-paste DNA transposon Sleeping Beauty (SB) is widely used for genome engineering, mutagenesis and gene delivery. When mobilized from a genomic donor position (“launch site”), SB preferentially reintegrates locally (< 2 Mb), but factors governing its transposition from genomic sites remain incompletely understood. Here we analysed local transposition experiments in mouse embryonic stem cells to determine the influence of chromatin context and transposon cargo on SB transposition. Transposons in launch sites with transcriptionally active, accessible chromatin showed lower transposition efficiency. Large cargo and cargo with higher transcriptional activity also result in reduced transposition efficiency. After excision, local reintegration patterns closely resembled 3D contact frequencies of the launch site. This indicates that chromosome folding is a major determinant of the transposition pattern. Surprisingly, we did not detect any effect of the destination chromatin composition on reintegration efficiency. Cargo sequence modified the reintegration patterns: promoter-containing cargo increased both very proximal (<10kb) and interchromosomal transpositions, while CTCF binding sites in the cargo increased reintegration on the launch chromosome. Together, these results define key determinants of SB transposition in chromosomes and inform the design of SB-based genome engineering strategies.
• Longitudinal Gene Expression Profiling Reveals Molecular Evolution and Transcriptional Reprogramming During Multiple Myeloma Relapse
  GSE352244Homo sapiens105 个样本2026-10-31

  This study aims to characterize gene expression alterations associated with multiple myeloma (MM) relapse by performing longitudinal gene expression profiling (GEP) of CD138+ plasma cells isolated from bone marrow mononuclear cells collected from 35 patients at baseline, first relapse, and second relapse.
• Investigating the transcriptional response of PSC2 deletion and overexpression in C. neoformans
  GSE352234Cryptococcus neoformans6 个样本2026-10-31

  Adaptation to CO2 is necessary for virulence in Cryptococcus neoformans. The regulation of Ace2p activity and cellular morphogenesis (RAM) pathway is essential for growth under high temperature and high CO2 conditions. We identified PSC2 (CNAG_01335) as a suppressor of the RAM pathway in H99 cbk1 deletion mutant. To investigate the role of Psc2, RNA sequencing was performed on the wild-type H99, PSC2 deletion, and Psc2 over expression strains.
• Age-associated hsa_piR_020485 inhibits osteogenic differentiation of bone marrow stromal cells and promotes macrophage migration
  GSE351871Rattus norvegicus6 个样本2026-10-31

  Age-related decline in bone marrow stromal cell (BMSC) function and inflammatory changes contribute to osteoporosis. We investigated the age-associated PIWI-interacting RNA hsa_piR_020485 and its effects on BMSC function, macrophage responses, and trabecular bone volume fraction.
• Proteasomes in extracellular vesicles mediate most transcriptional effects in recipient colorectal cancer cells
  GSE351755Homo sapiens28 个样本2026-10-31

  Extracellular vesicles (EVs) transmit lipids, proteins and RNA between cells of the organism. Among their cargo, EVs contain different forms of proteasomes - multi-subunit protein complexes responsible for degradation of most intracellular proteins. The transmission of proteasomes by EVs from one cell to another has been recently shown; however the biological significance of the phenomenon is generally unknown. Here we purified EVs from control colorectal adenocarcinoma cells and cells treated with IFN-γ, a cytokine known to activate expression of specific proteasome forms - non-constitutive proteasomes (ncPs). The obtained vesicles were incubated with two different irreversible proteasome inhibitors: carfilzomib and ONX-0914, targeting all forms and specifically ncPs, correspondingly. EVs were then incubated with control or carfilzomib-treated colorectal adenocarcinoma cells and the cellular RNA was obtained, followed by transcriptome acquisition and analysis. Incubation of control and carfilzomib-treated cells with treated or non-treated EVs obtained from control donor cells induced almost no effect on gene expression in recipient cells. However, vesicles obtained from IFN-γ-treated cells modulated expression of 53 genes in control cells and 2 genes in carfilzomib-treated cells. Treatment of vesicles with either one or another proteasome inhibitor affected the expression of 49 genes in control cells. In carfilzomib-treated cells inhibition of proteasomes in EVs affected 21 genes. Importantly, in both cases inhibition of ncPs in vesicles using ONX-0914 induced more pronounced effects on transcription in recipient cells. Most of the genes with differential expression were involved in oxidative phosphorylation. Obtained results indicate that most of the effects mediated in recipient cells by EVs were associated with the activity of proteasomes and specifically non-constitutive proteasomes, highlighting novel insights into EVs mediated proteasome transfer.
• Overexpression of IL-1Ra in MSCs Ameliorates Hepatic Injury via GGT5 and Improves Survival of aGVHD Mice
  GSE351748Homo sapiens6 个样本2026-10-31

  In conclusion, oeIL_x001E_1Ra_x001E_MSCs alleviate aGVHD_x001E_related hepatic lesions through anti_x001E_inflammatory effects and GGT5_x001E_dependent maintenance of redox and mitochondrial homeostasis, offering a promising cell_x001E_therapy strategy and theoretical foundation for targeted treatment of hepatic aGVHD.
• Liver Kinase B1 depletion disrupts the pantothenic acid: coenzyme A pathway in astrocytes
  GSE351587Mus musculus8 个样本2026-10-31

  Previous studies showed conditional knockout of Liver Kinase B1 (LKB1) from astrocytes exacerbated disease severity and glial cell activation in a mouse model of Multiple Sclerosis (MS). A major function of LKB1 is to maintain energy supplies under conditions of metabolic stress, suggesting that loss of LKB1 could alter astrocytic metabolic processes. Following siRNA mediated knockdown (KD) of LKB1 from primary mouse astrocytes, untargeted metabolomic screening identified significant increases in Pantothenic Acid (PA) and related metabolites; and pathway analysis showed the PA:Coenzyme A (PA:CoA) pathway was significantly modified. This pathway was also identified by bulk RNA sequencing. In LKB1 KD cells, relative mRNA levels of enzymes in the PA:CoA pathway were reduced, and PA Kinase 2 (Pank2, which converts PA to phosphoPA) expression was reduced. Deficiencies in Pank2 are known to cause iron accumulation, which we confirmed occurs in LKB1 KD astrocytes. The KD cells also showed increased sensitivity to induction of ferroptosis. Measurement of serum PA levels showed a positive correlation with age at diagnosis in relapsing remitting MS patients harboring a variant in the gene encoding LKB1. Together, these results indicate that metabolic disturbance leads to dysregulation of the PA:CoA pathway in astrocytes and suggest that plasma PA levels could provide a novel biomarker for MS disease.
• Twenty-Hour Hypothermic Oxygenated Perfusion Preserves Myocardial Viability and Bioenergetics with No Primary Graft Dysfunction After Porcine Heart Transplantation
  GSE351179Sus scrofa8 个样本2026-10-31

  Background: Hypothermic oxygenated perfusion (HOPE) may extend donor heart preservation beyond conventional storage durations. We evaluated early graft function and myocardial cellular and metabolic integrity following porcine heart transplantation after 20 hours of HOPE. Methods: Ten donor hearts underwent various preservation conditions: static cold storage (SCS) for 4 hours (n=2), HOPE for 4 hours (n=3), and HOPE for 20 hours (n=5), followed by heart transplantation (HT) in recipient pigs. Following implant and reperfusion, graft function was assessed over 3 hours by serial echocardiography, invasive hemodynamics, optical flow analysis, and vasoactive support scoring; myocardial tissue was analyzed by histopathology, flow cytometry, mitochondrial respirometry, transcriptomics, and proteomics. Results: Ejection fraction, right atrial pressure and systolic blood pressure did not differ significantly between groups, and no graft met criteria for primary graft dysfunction. LV contractility was within normal range with comparable vasoactive support among all groups. Preservation-associated weight gain was greatest after HOPE 20h, and histopathology showed comparable findings with edema present in all cohorts, without fibrosis, thrombosis, or necrosis. Cardiomyocyte viability was preserved across all groups (HOPE 20h, 86%, HOPE 4h, 81%, and SCS 4h, 77%). Maximal oxygen consumption rate was elevated in HOPE 20h versus HOPE 4h and SCS 4h (p<0.01), while basal and non-mitochondrial respiration were similar. Transcriptomics and proteomics revealed minimal differences in gene and pathway expression among groups. Conclusions: HOPE preserves donor heart viability, mitochondrial integrity, and ventricular function after 20 hours of ischemia in a porcine model, without evidence of primary graft dysfunction, supporting extended preservation for heart transplantation. Edema, recovery of function, and metabolic responses warrant further investigation with longer-term monitoring.
• Parallel transcriptomics reveals insect developmental shifts and gall-associated host transcriptional differences in Quadrastichus erythrinae and Erythrina variegata
  GSE351178Erythrina variegata; Quadrastichus erythrinae12 个样本2026-10-31

  Gall development involves changes in insect development and host tissue gene expression. This study used separate RNA-seq comparisons of Quadrastichus erythrinae larvae and pupae and of galled and ungalled Erythrina variegata petioles collected from one host tree during one sampling occasion. Insect reads were analyzed against a reference genome, while plant reads were assembled de novo and analyzed using a frozen sequence-provenance exclusion mask. Differential expression and annotation-based candidate analyses were used to describe developmental-stage differences in the insect and gall-associated transcriptional differences in the host. The comparisons support candidate functional themes for further investigation and do not directly test molecular interactions between the organisms.
• Spatial transcriptomic analysis of fibroblast therapy with collagen/PMMA in human skin [Xenium]
  GSE350895Homo sapiens3 个样本2026-10-31

  Xenium spatial transcriptomic analysis was performed to investigate cellular responses and tissue remodeling following fibroblast therapy with or without collagen/PMMA in human skin.

  空间转录组
• Collagen-PMMA scaffolds induce dermal remodeling and immune recruitment distinct from simple volar fibroblast therapy in human skin [scRNAseq]
  GSE350894Homo sapiens3 个样本2026-10-31

  Cellular therapy is promising but requires optimization in human subjects. Volar skin of the palms and soles is adapted to mechanical stress through a thick epidermis and dense extracellular matrix, whereas non-volar skin is vulnerable at high-pressure sites such as prosthetic limb interfaces. Because volar fibroblasts can partially reprogram non-volar skin, we tested whether collagen/polymethyl methacrylate (PMMA) could enhance volar fibroblast therapy. Healthy volunteers received vehicle, scalp fibroblast, or volar fibroblast injections, with or without collagen/PMMA, into non-volar skin. Durometer, optical coherence tomography, histology, and transcriptomic analyses showed volar-like structural changes and activation of skin-development, keratinocyte-differentiation, extracellular-matrix, and morphogenesis pathways. Collagen/PMMA promoted fibroblast, immune, and endothelial cell accumulation, consistent with a scaffold-associated tissue response. These findings distinguish volar fibroblast–associated skin identity changes from collagen/PMMA-induced stromal remodeling with foreign body, inflammatory, and fibrotic/myofibroblast-associated features.

  单细胞
• Single-cell analysis reveals sex-specific ERβ regulation of neurovascular protection in the AppNL-G-F mouse model of Alzheimer’s disease
  GSE350656Mus musculus4 个样本2026-10-31

  Alzheimer’s disease (AD) exhibits pronounced sex differences, but the molecular mechanisms underlying this dimorphism remain unclear. To investigate the role of estrogen receptor beta (ERβ; Esr2) in modulating sex-specific amyloid pathology, single-cell RNA sequencing was performed on hippocampal tissue from six-month-old male and female AppNL-G-F and AppNL-G-F/Esr2KO mice. Loss of Esr2 induced sex-dependent alterations in amyloid burden, glial activation states, and endothelial-centered intercellular communication networks, with more pronounced transcriptomic remodeling in males. Transthyretin (Ttr) emerged as a strongly sex-modulated gene associated with increased amyloid pathology in male Esr2-deficient mice. These data provide a sex-stratified transcriptomic resource for understanding ERβ-dependent regulation of cellular programs in AD-related pathology

  单细胞
• Tidal ventilation induces divergent repair responses in lung epithelial cells and fibroblasts mediated by IL-6 signaling
  GSE350588Homo sapiens24 个样本2026-10-31

  Mechanical ventilation may alter lung repair by differentially regulating epithelial and fibroblast responses. This study investigated transcriptional responses in human bronchial epithelial cells (BEAS-2B) and lung fibroblasts (MRC-5) exposed to bronchoalveolar lavage fluid from patients receiving tidal mechanical ventilation or continuous positive airway pressure (CPAP). Following scratch injury, cells were cultured with bronchoalveolar lavage fluid, with or without the IL-6 receptor inhibitor tocilizumab, and profiled using the Ion AmpliSeq Transcriptome Human Gene Expression Panel on an Ion S5 Prime sequencer. Differential gene expression and pathway analyses identified distinct responses associated with ventilatory condition, including altered inflammatory signaling and epithelial repair programs in BEAS-2B cells and increased extracellular matrix remodeling and profibrotic signaling in MRC-5 fibroblasts. IL-6 receptor blockade attenuated ventilation-associated transcriptional differences in both cell types. These data support a role for IL-6 signaling in the divergent epithelial and fibroblast repair responses associated with mechanical ventilation.
• SARS-CoV-2 Nsp2 reprograms host immunity to drive pathogenic inflammation
  GSE350427Mus musculus; Severe acute respiratory syndrome coronavirus 236 个样本2026-10-31

  Despite the end of the COVID-19 pandemic, SARS-CoV-2 continues to circulate endemically, highlighting the need to better understand the viral determinants of pathogenesis. Putative functions of the non-structural protein 2 (Nsp2) have been studied in vitro but how Nsp2 affects pathogenesis and overall viral fitness in vivo has yet to be demonstrated. Here, we generated a recombinant SARS-CoV-2 lacking Nsp2 (ΔNsp2) to investigate its role in viral replication and disease. While ΔNsp2 replicated comparably to wild-type virus in vitro and in vivo, its deletion resulted in markedly attenuated disease in K18-hACE2 mice. Wild-type virus infection induced a strong pro-inflammatory response associated with increased recruitment of monocytes and macrophages, whereas ΔNsp2 virus infection promoted a more balanced antiviral response characterized by enhanced lymphocyte and NK cell recruitment. This was accompanied by reduced pulmonary and systemic inflammation and distinct transcriptional programs, including downregulation of pathways related to RNA processing and translation. Mechanistically, CLIP-seq and proximity labeling suggest that Nsp2 interacts with host RNA and components of the translational machinery. Together, our findings identify Nsp2 as a key virulence factor that drives immunopathology by skewing host immune responses, highlighting its role as a regulator of host–pathogen interactions.
• Gene Expression in the Glioblastoma Cell Line (GL261) Transcriptome Following Treatment with Magnetic Nanoparticles (MNPQ)
  GSE349688Mus musculus9 个样本2026-10-31

  GL261 cells are a widely used glioma tumor model system; following in situ transplantation, they stably form glioblastoma and are extensively utilized as a preclinical evaluation model for brain gliomas. Magnetic nanomedicines (MNPQ), with their advantages of magnetically responsive targeted enrichment and locally controlled release, have demonstrated effective antitumor potential against gliomas; however, how they reshape the gene expression profile of tumor cells at the transcriptomic level remains unclear. Our study has one primary objective: to identify differentially expressed genes and their enriched signaling pathways in the GL261 cell transcriptome before and after MNPQ treatment, thereby elucidating the molecular mechanisms underlying its antitumor effects.