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1. ⭐ GSE312646 TRC-051384激活热休克通路保护螺旋神经节神经元免受噪声引起的听力损失[空间转录组学]

• ✍️ 作者：未知作者
• 🏷️ 关键词：spatial、spatial transcriptomics、transcriptomics、pathway
• 📝 描述：Contributors : Jeffrey N Savas ; Seby Edassery ; Miguel RamirezSeries Type : OtherOrganism : Mus musculusNoise-induced hearing loss (NIHL) is a major public health problem caused by damage to cochlear hair cells, synapses, and spiral ganglion neurons (SGNs). However, effective treatments are completely lacking. We investigated cellular stress responses induced by loud noise in a mouse model of cochlear synaptopathy and tested whether selective activation of the dominant pathway identified could confer protection. RNA sequencing and spatial transcriptomics revealed that noise exposure elicited a robust but transient upregulation of endoplasmic reticulum chaperones and proteasome subunits in SGNs and supporting cells. To target this response, we administered TRC051384, a small-molecule activator of the heat shock transcription factor Hsf1, prior to noise exposure. TRC051384 crossed the blood–labyrinth barrier and reached the cochlea, induced heat shock protein gene expression, and restored ubiquitin–proteasome function in SGNs. Notably, TRC051384 treatment improved auditory brainstem response recovery, preserved Wave I amplitudes, and maintained ribbon synapse density. These findings establish proteotoxic stress in SGNs as a central driver of NIHL and identify HSF1 activation as a promising therapeutic strategy.
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2. GSE312570 灵长类肠道菌群诱导小鼠神经发育中具有进化意义的变化

• ✍️ 作者：未知作者
• 🏷️ 关键词：gut、regex:gut(-?microbiome)?
• 📝 描述：Contributors : Alex DeCasien ; Jacob Arnoff ; Elizabeth Mallot ; Sahana Kuthyar ; Sriram Chitta ; Brian Layden ; Maria Savo Sardaro ; Stanton Grey ; Lawrence Williams ; Emma Leichty ; Hyo Lee ; Won Lee ; James Curly ; Christopher Kuzawa ; Katherine AmatoSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusMultiple primate species, including humans, evolved brains that are exceptionally large relative to their body sizes. These large brains coevolved with metabolic adaptations that enhance cerebral energy supply, including increased circulating glucose levels. While the gut microbiota (GM) is known to influence host metabolism, its potential role in primate brain evolution remains unclear. To investigate this, we inoculated germ-free mice with the GMs of primate species selected to separate the effects of brain size (encephalization) from phylogenetic relatedness: humans (large-brained, Catarrhini), macaques (smaller-brained, Catarrhini), and squirrel monkeys (large-brained, Platyrrhini). We first show that differences in brain gene expression between mice inoculated with human versus macaque GMs resemble those observed between actual human and macaque brains. Comparing the effects of the different primate GMs on mouse brain gene expression further revealed that, despite greater evolutionary distance, the GMs from the two larger-brained species (humans and squirrel monkeys) similarly upregulated genes associated with energy production. Notably, human GMs specifically increased the expression of genes involved in oxidative phosphorylation, and these gene expression changes correlated with increased abundances of GM metabolic pathways related to glucose metabolism and gluconeogenesis. Human GMs also downregulated evolutionarily conserved genes implicated in neurodevelopmental disorders such as autism. Although these are findings based on a small sample of primate species and must be interpreted as preliminary, they suggest that species differences in GM composition can influence brain metabolism and raise the possibility that the GM could have played a supporting role in primate encephalization.
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3. GSE312384 BACH2 调控 T 细胞谱系状态以增强 CAR T 细胞功能 [ATAC-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：T cell、ATAC-seq
• 📝 描述：Contributors : Tien-Ching Chang ; John M Warrington ; Nathan A SinghSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensNearly all chimeric antigen receptors (CARs) signal in the absence of antigen, referred to as “tonic signaling”. Tonic signaling of CARs containing the CD28 costimulatory domain has been shown to driveT cell exhaustion; in contrast, we found that tonic signaling of 41BB-containing CARs enhances T cell function. Using a panel of CARs targeting CD22, we identified that tonic 41BB signaling activatesBACH2, a transcriptional regulator that directs stem and memory programs. Overexpression of BACH2 prevented tonic CD28-driven exhaustion but locked CAR T cells in quiescent states. To overcome this, we linked BACH2 to a degradation domain and found that tuning BACH2 expression enhanced long-term efficacy of exhaustion-prone CAR T cells targeting liquid and solid tumors. Through interrogation of CAR products, we also found an association between BACH2 activity and clinical outcomes in patients with leukemia. These data identify a central role for BACH2 in regulating CAR T cell efficacy.
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4. GSE312224 小鼠耳蜗血管纹内皮细胞和周细胞群的单细胞RNA测序

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq、single-cell
• 📝 描述：Contributors : Zhiqiang Hou ; Yunpei Zhang ; Jinhui Zhang ; Pingting Wang ; Xiaorui ShiSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe cochlear stria vascularis (SV) maintains the endocochlear potential and relies on specialized vascular endothelial cells and pericytes. To characterize the transcriptional profiles of these vascular populations at single-cell resolution, we performed single-cell RNA sequencing (scRNA-seq) on SV tissue from reporter mice. SV was microdissected from temporal bones of 1–3 month-old Tie2-GFP (endothelial reporter) and NG2-DsRed (pericyte reporter) mice, enzymatically dissociated to obtain single-cell suspensions, and, when applicable, subjected to FACS enrichment for Tie2-GFP–positive endothelial cells or NG2-DsRed–positive pericytes. Viable cells were loaded onto the 10x Genomics Chromium platform for single-cell capture and 3′ barcoded library preparation. This dataset contains two independent batches corresponding to SV endothelial cell–enriched and pericyte-enriched preparations and enables analysis of vascular heterogeneity within the mouse stria vascularis.
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5. GSE300895 高分辨率空间转录组学结合基于深度学习的图像分割技术，实现了对特发性肾病综合征患者的存档FFPE肾脏组织进行单细胞空间分析。

• ✍️ 作者：未知作者
• 🏷️ 关键词：single-cell、spatial
• 📝 描述：Contributors : Simen F Pettersen ; Eleni Skandalou ; Jessica Furriol ; Tarig Osman ; Hans-Peter Marti ; Øystein S EikremSeries Type : OtherOrganism : Homo sapiensWe have perfomed Visium HD spatial transcriptomics on archival FFPE kidney biopsies from patients with different manifistations of nephrotic syndrome, i.e., steriod sensitive, frequent relapsing and/or steroid dependent, and focal segmental glomerulosclerosis. Using a pre-trained deep learning model from StarDist to segment nuclei, we reconstructed single-nucleus level spatial trancriptomic datasets through custom binning of subcellular capture areas. We integrated the datasets from the different patients and indentified conserved cell types. Moreover, we identified patient specific transcriptomic differences in the podocyte cell population. This article demonstrates the usefullness of this approach to future studies of pathophysilogical mechanisms in idiopathic nephrotic syndrome.
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6. GSE292096 NFAT介导胰腺导管腺癌中癌相关成纤维细胞的促肿瘤炎症[小鼠VIVIT]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、inflammation
• 📝 描述：Contributors : Chuner Guo ; Michelle F Griffin ; Annah G Morgan ; Michael T Longaker ; Jeffrey A NortonSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusPancreatic ductal adenocarcinoma (PDAC) is characterized by a dense stroma, low immunogenicity, and resistance to therapy. Cancer-associated fibroblasts (CAFs) are key stromal cells within the tumor microenvironment (TME) that drive tumor progression. Interleukin-1 (IL-1) promotes fibrosis, pathogenic inflammation, and poor prognosis in PDAC. Using a novel single-cell multiomic approach, we investigate the IL-1 signaling axis in human and mouse models of PDAC, identifying nuclear factor of activated T cells (NFAT) transcription factors as key mediators. IL1R1+ CAFs activate an inflammatory phenotype associated with elevated NFAT motif activity and gene expression. In vivo, NFAT inhibition in a mouse model of PDAC significantly reduces tumor weight and fibrosis, supporting its pro-tumorigenic role. Our findings suggest that NFAT mediates IL-1-induced inflammation in PDAC, highlighting its potential as a therapeutic target. This study demonstrates the power of multiomic analyses to uncover therapeutic targets within the complex tumor microenvironment.
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7. GSE292095 NFAT 介导胰腺导管腺癌中癌相关成纤维细胞的促肿瘤炎症 [人类多组学]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、inflammation
• 📝 描述：Contributors : Chuner Guo ; Michelle F Griffin ; Annah G Morgan ; Michael T Longaker ; Jeffrey A NortonSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensPancreatic ductal adenocarcinoma (PDAC) is characterized by a dense stroma, low immunogenicity, and resistance to therapy. Cancer-associated fibroblasts (CAFs) are key stromal cells within the tumor microenvironment (TME) that drive tumor progression. Interleukin-1 (IL-1) promotes fibrosis, pathogenic inflammation, and poor prognosis in PDAC. Using a novel single-cell multiomic approach, we investigate the IL-1 signaling axis in human and mouse models of PDAC, identifying nuclear factor of activated T cells (NFAT) transcription factors as key mediators. IL1R1+ CAFs activate an inflammatory phenotype associated with elevated NFAT motif activity and gene expression. In vivo, NFAT inhibition in a mouse model of PDAC significantly reduces tumor weight and fibrosis, supporting its pro-tumorigenic role. Our findings suggest that NFAT mediates IL-1-induced inflammation in PDAC, highlighting its potential as a therapeutic target. This study demonstrates the power of multiomic analyses to uncover therapeutic targets within the complex tumor microenvironment.
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8. GSE292094 NFAT介导胰腺导管腺癌中癌相关成纤维细胞的促肿瘤炎症[小鼠多组学]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、inflammation
• 📝 描述：Contributors : Chuner Guo ; Michelle F Griffin ; Annah G Morgan ; Michael T Longaker ; Jeffrey A NortonSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusPancreatic ductal adenocarcinoma (PDAC) is characterized by a dense stroma, low immunogenicity, and resistance to therapy. Cancer-associated fibroblasts (CAFs) are key stromal cells within the tumor microenvironment (TME) that drive tumor progression. Interleukin-1 (IL-1) promotes fibrosis, pathogenic inflammation, and poor prognosis in PDAC. Using a novel single-cell multiomic approach, we investigate the IL-1 signaling axis in human and mouse models of PDAC, identifying nuclear factor of activated T cells (NFAT) transcription factors as key mediators. IL1R1+ CAFs activate an inflammatory phenotype associated with elevated NFAT motif activity and gene expression. In vivo, NFAT inhibition in a mouse model of PDAC significantly reduces tumor weight and fibrosis, supporting its pro-tumorigenic role. Our findings suggest that NFAT mediates IL-1-induced inflammation in PDAC, highlighting its potential as a therapeutic target. This study demonstrates the power of multiomic analyses to uncover therapeutic targets within the complex tumor microenvironment.
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9. GSE292093 NFAT介导胰腺导管腺癌中癌相关成纤维细胞的促肿瘤炎症[小鼠模型]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、inflammation
• 📝 描述：Contributors : Chuner Guo ; Michelle F Griffin ; Annah G Morgan ; Michael T Longaker ; Jeffrey A NortonSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusPancreatic ductal adenocarcinoma (PDAC) is characterized by a dense stroma, low immunogenicity, and resistance to therapy. Cancer-associated fibroblasts (CAFs) are key stromal cells within the tumor microenvironment (TME) that drive tumor progression. Interleukin-1 (IL-1) promotes fibrosis, pathogenic inflammation, and poor prognosis in PDAC. Using a novel single-cell multiomic approach, we investigate the IL-1 signaling axis in human and mouse models of PDAC, identifying nuclear factor of activated T cells (NFAT) transcription factors as key mediators. IL1R1+ CAFs activate an inflammatory phenotype associated with elevated NFAT motif activity and gene expression. In vivo, NFAT inhibition in a mouse model of PDAC significantly reduces tumor weight and fibrosis, supporting its pro-tumorigenic role. Our findings suggest that NFAT mediates IL-1-induced inflammation in PDAC, highlighting its potential as a therapeutic target. This study demonstrates the power of multiomic analyses to uncover therapeutic targets within the complex tumor microenvironment.
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10. GSE275826 年轻和衰老真皮巨噬细胞的单细胞转录组比较

• ✍️ 作者：未知作者
• 🏷️ 关键词：single-cell
• 📝 描述：Contributors : Yu-Tung Li ; Saki IshinoSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusPreviously, in a meta-analysis of public single-cell transcriptomes profiling various healthy and disease tissues, we demonstrated that macrophage heterogeneity in skin, as well as in other mouse tissues, could be described into 5 distinct identities (S1-5) with a defined transcriptomic fingerprint, regardless of tissue origins. We established a general identity scheme for tissue macrophages, MIKA (Macrophage Identity Kinetics Archive) as an alternative to the conventional M1/M2 scheme which shows limitations in annotating in vivo tissue macrophages. (PMID: 39720957) MIKA was recently updated to finetune identity definition, and to include more tissues and pathophysiological conditions. (PMID: 41342690) Under the current MIKA framework, tissue macrophages are classified to 6 core identities (S1-S6, common to various tissues) and/or tissue-specific macrophages. This dataset is a part of the raw data sources of the latest version of MIKA profiling single-cell transcriptomes of F4/80+MHCII-hi macrophages FACS-isolated from dorsal skin of young (9 week-old) and old (108 week-old) C57BL/6 male mice.
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💡 该来源还有 13 条内容，详见 文末

• GSE312389 利用高选择性 T 细胞受体靶向生物制剂阐明共刺激信号在人类病毒特异性记忆 CD8+ T 细胞活化和扩增中的作用
• GSE312367 BACH2 调控 T 细胞谱系状态以增强 CAR T 细胞功能 [Cut & Run]
• GSE312344 产科抗磷脂综合征的全转录组分析
• GSE312323 鉴定对雌激素受体α结合及其对子宫内膜癌基因表达的影响具有独特影响的基因组特征 [SOX17_ChIPseq]
• GSE312322 鉴定对雌激素受体α结合及其对子宫内膜癌基因表达的影响具有独特影响的基因组特征 [CRISPRScreen]
• GSE312030 HRAS 和 MEK 联合抑制可诱导 HRAS 突变型横纹肌肉瘤的肿瘤消退并恢复其肌源性分化
• GSE312004 下丘脑CRH神经元激活触发脾细胞增殖并促进动脉粥样硬化
• GSE311964 Biop-C 能够检测植入前人类胚胎中平衡和非平衡重排的全基因组范围
• GSE288397 整合机器学习和转录组学以提高酵母中β-胡萝卜素的产量
• GSE286715 t6A tRNA 修饰定义了 RIG-I 介导的抗肿瘤免疫反应 [RNA-seq2]
• GSE286709 t6A tRNA 修饰定义了 RIG-I 介导的抗肿瘤免疫反应 [RNA-seq1]
• GSE286704 t6A tRNA修饰定义了RIG-I介导的抗肿瘤[Ribo-seq]免疫反应
• GSE283783 严重阻塞性睡眠呼吸暂停成年患者在 CPAP 治疗前后的甲基化分析。