详细内容（前10条）

1. ⭐ GSE301226 KRT6A 通过 RAB39B 激活自噬途径增强肺鳞状细胞癌的放射治疗抗性 [RNA-Seq 2]

• ✍️ 作者：未知作者
• 🏷️ 关键词：carcinoma、resistance、RNA-seq、pathway
• 📝 描述：Contributors : Zaishuang Ju ; Yutong Wu ; Zhiqi Zheng ; Eric W Lam ; Dachuan Shen ; Ruoyu WangSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAbstract Background: Radiotherapy is the cornerstone for lung squamous cell carcinoma (LUSC) treatment, yet its efficacy is often limited by the development of radioresistance. Understanding the molecular mechanisms driving this resistance is critical for improving therapeutic outcomes. Results: In this study, we established a radioresistant LUSC cell line and identified KRT6A as a pivotal gene involved in radiotherapy resistance. Transcriptome sequencing and further validation revealed RAB39B as a downstream target of KRT6A. The KRT6A-RAB39B axis promotes radioresistance by activating the autophagy pathway, enhancing cancer cell survival in response to radiation stress. Mechanistic studies confirmed that KRT6A regulates autophagy through modulation of RAB39B expression. Conclusions：This work is the first to uncover a role of the KRT6A-RAB39B axis in LUSC radioresistance, offering new insights into the mechanisms and potential targets underlying radiotherapy failure.
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2. ⭐ GSE301225 KRT6A 通过 RAB39B 激活自噬途径增强肺鳞状细胞癌的放射治疗抗性 [RNA-Seq 1]

• ✍️ 作者：未知作者
• 🏷️ 关键词：carcinoma、resistance、RNA-seq、pathway
• 📝 描述：Contributors : Zaishuang Ju ; Yutong Wu ; Zhiqi Zheng ; Eric W Lam ; Dachuan Shen ; Ruoyu WangSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAbstract Background: Radiotherapy is the cornerstone for lung squamous cell carcinoma (LUSC) treatment, yet its efficacy is often limited by the development of radioresistance. Understanding the molecular mechanisms driving this resistance is critical for improving therapeutic outcomes. Results: In this study, we established a radioresistant LUSC cell line and identified KRT6A as a pivotal gene involved in radiotherapy resistance. Transcriptome sequencing and further validation revealed RAB39B as a downstream target of KRT6A. The KRT6A-RAB39B axis promotes radioresistance by activating the autophagy pathway, enhancing cancer cell survival in response to radiation stress. Mechanistic studies confirmed that KRT6A regulates autophagy through modulation of RAB39B expression. Conclusions：This work is the first to uncover a role of the KRT6A-RAB39B axis in LUSC radioresistance, offering new insights into the mechanisms and potential targets underlying radiotherapy failure.
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3. ⭐ GSE335775 单细胞 RNA 测序揭示小鼠代谢功能障碍相关脂肪性肝炎中内皮细胞 STING 依赖性免疫重塑

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune、metabolic、sequencing、single-cell
• 📝 描述：Contributors : Zhi-Bin Lin ; Peng Zou ; Xian-Yi Ma ; Jun-Bo Song ; Hong Zhang ; Wei Du ; Dan Wei ; Ping Song ; Xin Hong ; Jing-Jing Liu ; Zhi-Qiang Fang ; Hao Xu ; Fei He ; Juan-Li Duan ; Ke-Feng Dou ; Lin WangSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusLiver sinusoidal endothelial cells (LSECs) regulate nutrient flux and immune surveillance within the hepatic niche. Here, we investigate how endothelial-intrinsic cGAS-STING signaling integrates metabolic stress signals to reshape adaptive immune responses in metabolic dysfunction-associated steatohepatitis (MASH) at single-cell resolution. We performed single-cell RNA sequencing on liver tissues from endothelial cell-specific Sting knockout mice (Stingfl/fl Cdh5-Cre+) and littermate controls (Stingfl/fl Cdh5-Cre-) subjected to a western diet combined with CCl4 (WD-CCl4) for 12 weeks. Unbiased cell-type annotation revealed broad immune remodeling following LSEC-STING deletion. Among CD4+ T cells, LSEC-STING deletion resulted in a marked reduction of pathological Th17 cells, accompanied by expansion of regulatory T cells (Tregs), leading to a significantly increased Treg/Th17 ratio. LSEC-STING deletion also reduced exhausted CD8+ T cells while increasing effector CD8+ T cells. Mechanistically, LSEC-intrinsic STING signaling represses BMP4 transcription through NF-kB-mediated competition with AP-1, disrupting a tolerance-supporting angiocrine program. These findings identify endothelial STING as a vascular immunometabolic checkpoint that links chronic metabolic stress to adaptive immune remodeling in MASH.
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4. ⭐ GSE336556 空间转录组学揭示稳定和排斥的人类肺同种异体移植中支气管相关淋巴组织组成的差异

• ✍️ 作者：未知作者
• 🏷️ 关键词：spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributors : Alexander Wein ; Changxu Fan ; Vladimir Sukhov ; Junedh Amrute ; Jon Ritter ; Amit Bery ; Maxim Artyomov ; Alexander Krupnick ; Ruben Nava ; Andrew Gelman ; Kory Lavine ; Daniel KreiselSeries Type : OtherOrganism : Homo sapiensBackground: Lung allograft rejection is determined by pathologist grading of transbronchial biopsies (TBBx) according to criteria established by the International Society of Heart and Lung Transplantation (ISHLT). Lymphocytic bronchiolitis (LB), described as mononuclear cells in bronchiolar submucosa, exhibits significant histologic overlap with bronchus-associated lymphoid tissue (BALT) leading to diagnostic uncertainty. Additionally, the role of BALT in tolerance and rejection is debated. We sought to characterize lymphoid aggregates in ISHLT acute cellular rejection (ACR) grades A0 or A3 biopsies to better understand the spectrum of BALT and rejection lesions. Methods: TBBx were reviewed for the presence of BALT. Representative A0 and A3 biopsies were selected for spatial transcriptomics and multiplex immunofluorescence microscopy. Results: Spatial transcriptomics of allograft biopsies enabled unbiased identification of BALT and rejection lesions via neighborhood analysis. CXCL9/10+ T and PDL1/L2+ myeloid cell clusters were enriched in A0 BALT, while an NKG7+CD8+ T cell cluster was enriched in A3 BALT. Higher expression of CXCL9 and CXCL10 in the BALT correlated with A0 grade. Computational methods identified occult areas of lymphoid aggregates in rejecting lung parenchyma with similarity to rejection lesions. A3 BALT and rejection lesions showed substantial similarities. Immunofluorescence confirmed the key transcriptomics findings. Conclusions: This study suggests a relationship between the immune microenvironment in BALT and graft rejection. Additionally, lymphoid infiltration in allografts graded A3 may be more widespread than apparent on Hematoxylin and Eosin (H&E) stain.
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5. GSE318225 开发一种优化的表观遗传沉默剂以转录失活慢性乙型肝炎中的病毒DNA [RNA测序]

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNAseq、epigenetic
• 📝 描述：Contributors : Yesseinia Anglero-Rodriguez ; Qiang Xiong ; Sarah B Voytek ; Glen Acosta ; Rayman Choo-Wing ; Lenka Hoffman ; Arogya Khadka ; Jhon Medina ; Caroline Mugambwa ; Chloe Pantano ; Sivan Harel ; Amber DiPiazza ; Sameer Abraham ; Erica M Hildebrand ; Ricardo N Ramirez ; Ava Zhai ; Xiaoyun Guo ; Sahar Abubucker ; Chih-Wei Ko ; Cristiana Giancarlo ; Bradley Niesner ; Martino Alfredo Cappelluti ; Matteo Conti ; Lorena Donnici ; Pietro Spinelli ; Taesun Eom ; Mary S Morrison ; Ari E Friedland ; Raffaele De Francesco ; Angelo Lombardo ; Vic E Myer ; Aron B Jaffe ; Melissa Bonner ; Jennifer L MarloweSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensApproved chronic hepatitis B (CHB) therapies rarely result in functional cure, as they fail to permanently silence all transcriptionally active hepatitis B virus (HBV) DNA. CRMA-1001 employs an optimized epigenetic silencer that represses viral transcription through targeted deposition of DNA methylation on episomal and integrated HBV DNAs. In HBV mouse models, a single dose of CRMA-1001 produced >3 log10 reductions in viral biomarkers, which correlated with de novo methylation of HBV DNA. Three doses resulted in up to 90% of animals with undetectable hepatitis B surface antigen (HBsAg) and HBV DNA by 6 months post-treatment. In non-human primates, CRMA-1001 induced transient liver transaminase elevations only at the highest dose tested. Expression and DNA methylation profiling revealed no detectable unintended targets in the human genome. These findings support the initiation of clinical development of CRMA-1001 as a finite treatment course with the potential for functional cure in individuals living with CHB.
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6. GSE336573 异常的 OGT 内含子滞留将磷酸酶功能障碍与 O-GlcNAc 崩解和神经元脆弱性联系起来 [脑类器官 RNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：Neuronal、RNA-seq
• 📝 描述：Contributors : Liu Yue ; Ki Myeong Na ; Mi-Ran Song ; Sung-Kyun ParkSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBackgroundImpaired protein phosphatase 2A (PP2A) activity, altered RNA processing, and reduced O-GlcNAcylation are recurrent features of Alzheimer’s disease (AD), but how these processes are mechanistically linked remains unclear. Because PP2A has been implicated in RNA processing control and O-GlcNAc transferase (OGT) is both the enzyme that maintains O-GlcNAc homeostasis and a transcript regulated at the level of RNA processing, we investigated whether PP2A inhibition promotes maladaptive OGT RNA processing under AD-like stress.MethodsSustained phosphatase dysfunction was modeled using okadaic acid in neuronal cell lines and human cerebral organoids. Time-resolved biochemical, transcriptional, and functional analyses were used to define the sequence linking Tau phosphorylation, OGT RNA processing, OGT expression, O-GlcNAcylation, and neuronal survival upon PP2A inhibition. OGT intron retention was perturbed using antisense oligonucleotides and CRISPR/Cas9-mediated deletion of the OGT intronic splicing silencer (ISS), followed by functional, transcriptomic, and proteomic profiling. Public AD transcriptomic datasets were reanalyzed to assess disease relevance. RNA pulldown coupled to mass spectrometry and siRNA-mediated perturbation were used to identify PP2A-responsive factors associated with the OGT-ISS region.ResultsPP2A inhibition rapidly induced Tau hyperphosphorylation but subsequently triggered collapse of O-GlcNAc homeostasis, accompanied by β-catenin destabilization and neuronal death. Mechanistically, PP2A inhibition induced an aberrant OGT RNA-processing response characterized by increased OGT intron retention, reduced fully spliced OGT mRNA, and subsequent loss of OGT protein and global O-GlcNAcylation. Human AD datasets likewise showed reduced OGT expression together with increased retained-intron signal at the OGT locus. Suppression of OGT intron retention by antisense oligonucleotides improved survival under PP2A inhibition despite only limited recovery of OGT protein or bulk O-GlcNAcylation. CRISPR/Cas9-mediated deletion of the OGT intronic splicing silencer (ISS) prevented stress-induced OGT intron retention, preserved OGT expression and O-GlcNAc homeostasis, and conferred marked resistance to neurotoxicity. Beyond these effects, ISS deletion was accompanied by broader transcriptomic and…
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7. GSE336572 异常的 OGT 内含子保留将磷酸酶功能障碍与 O-GlcNAc 崩溃和神经元脆弱性联系起来 [SH-SY5Y RNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：Neuronal、RNA-seq
• 📝 描述：Contributors : Liu Yue ; Ki Myeong Na ; Sung-Kyun ParkSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBackgroundImpaired protein phosphatase 2A (PP2A) activity, altered RNA processing, and reduced O-GlcNAcylation are recurrent features of Alzheimer’s disease (AD), but how these processes are mechanistically linked remains unclear. Because PP2A has been implicated in RNA processing control and O-GlcNAc transferase (OGT) is both the enzyme that maintains O-GlcNAc homeostasis and a transcript regulated at the level of RNA processing, we investigated whether PP2A inhibition promotes maladaptive OGT RNA processing under AD-like stress.MethodsSustained phosphatase dysfunction was modeled using okadaic acid in neuronal cell lines and human cerebral organoids. Time-resolved biochemical, transcriptional, and functional analyses were used to define the sequence linking Tau phosphorylation, OGT RNA processing, OGT expression, O-GlcNAcylation, and neuronal survival upon PP2A inhibition. OGT intron retention was perturbed using antisense oligonucleotides and CRISPR/Cas9-mediated deletion of the OGT intronic splicing silencer (ISS), followed by functional, transcriptomic, and proteomic profiling. Public AD transcriptomic datasets were reanalyzed to assess disease relevance. RNA pulldown coupled to mass spectrometry and siRNA-mediated perturbation were used to identify PP2A-responsive factors associated with the OGT-ISS region.ResultsPP2A inhibition rapidly induced Tau hyperphosphorylation but subsequently triggered collapse of O-GlcNAc homeostasis, accompanied by β-catenin destabilization and neuronal death. Mechanistically, PP2A inhibition induced an aberrant OGT RNA-processing response characterized by increased OGT intron retention, reduced fully spliced OGT mRNA, and subsequent loss of OGT protein and global O-GlcNAcylation. Human AD datasets likewise showed reduced OGT expression together with increased retained-intron signal at the OGT locus. Suppression of OGT intron retention by antisense oligonucleotides improved survival under PP2A inhibition despite only limited recovery of OGT protein or bulk O-GlcNAcylation. CRISPR/Cas9-mediated deletion of the OGT intronic splicing silencer (ISS) prevented stress-induced OGT intron retention, preserved OGT expression and O-GlcNAc homeostasis, and conferred marked resistance to neurotoxicity. Beyond these effects, ISS deletion was accompanied by broader transcriptomic and proteomic rem…
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8. GSE335424 批量 RNA 测序揭示小鼠代谢功能障碍相关脂肪性肝炎中内皮细胞 STING 依赖性转录程序

• ✍️ 作者：未知作者
• 🏷️ 关键词：metabolic、sequencing
• 📝 描述：Contributors : Zhi-Bin Lin ; Peng Zou ; Xian-Yi Ma ; Jun-Bo Song ; Hong Zhang ; Wei Du ; Dan Wei ; Ping Song ; Xin Hong ; Jing-Jing Liu ; Zhi-Qiang Fang ; Hao Xu ; Fei He ; Juan-Li Duan ; Ke-Feng Dou ; Lin WangSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusLiver sinusoidal endothelial cells (LSECs) regulate nutrient flux and immune surveillance within the hepatic niche. Here, we investigate how endothelial-intrinsic cGAS-STING signaling integrates metabolic stress signals to reshape the hepatic niche in metabolic dysfunction-associated steatohepatitis (MASH). We performed bulk RNA sequencing on liver tissues from endothelial cell-specific Sting knockout mice (Stingfl/fl Cdh5-Cre+) and littermate controls (Stingfl/fl Cdh5-Cre-) subjected to a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 10 weeks. Gene set enrichment analysis revealed that multiple cancer-associated and fibrogenic signaling pathways were enriched in control livers but markedly suppressed in StingΔEC livers. Conversely, pathways related to T cell regulation and metabolism were preferentially enriched in StingΔEC livers, indicating that endothelial-intrinsic STING signaling drives MASH progression by reshaping T cell-mediated immune responses.
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9. GSE300663 组胺 H4 受体拮抗剂可阻止受体介导和 EBV 诱导的 B 细胞增殖 [ATAC-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：B cell、ATAC-seq
• 📝 描述：Contributors : Marlène Roy ; Émilie Bardel ; Amel Chebel ; Fabrice Chatonnet ; Pierre-Olivier Vidalain ; Patrice André ; Laurent GenestierSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensEpstein-Barr virus (EBV) infects over 90% of the global population and establishes lifelong latency in memory B cells. In healthy individuals, this latent infection is typically kept in check by the immune system. However, in immunosuppressed patients, EBV can reactivate, leading to uncontrolled B cell proliferation and development of post-transplant lymphoproliferative disorders (PTLD)—a potentially fatal complication. In this study, we demonstrate that selective antagonists of the histamine H4 receptor (H4R), a G protein-coupled receptor expressed in immune cells, potently suppress B cell activation and proliferation triggered by antigenic stimuli or EBV infection. Notably, the lead compound A943931 inhibited transcriptional programs critical for B cell activation, including downregulation of key metabolic genes, resulting in profound suppression of both glycolysis and oxidative phosphorylation. A943931 also blocked EBV-driven B cell immortalization and impaired energy metabolism in lymphoblastoid cell lines, albeit to a lesser extent than in receptor-stimulated B cells. In vivo, A943931 suppressed tumor growth in Daudi Burkitt lymphoma xenografts and prevented B cell lymphoma development in EBV-infected humanized mice. These findings reveal a novel immunometabolic vulnerability of EBV-infected B cells and position H4R antagonists as promising therapeutic candidates for EBV-associated lymphoproliferative disorders, including PTLD and potentially EBV-linked autoimmune diseases.
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10. GSE319073 开发一种优化的表观遗传沉默剂以转录失活慢性乙型肝炎中的病毒DNA [HBVMethylseq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：epigenetic
• 📝 描述：Contributors : Yesseinia Anglero-Rodriguez ; Qiang Xiong ; Sarah B Voytek ; Glen Acosta ; Rayman Choo-Wing ; Lenka Hoffman ; Arogya Khadka ; Jhon Medina ; Caroline Mugambwa ; Chloe Pantano ; Sivan Harel ; Amber DiPiazza ; Sameer Abraham ; Erica M Hildebrand ; Ricardo N Ramirez ; Ava Zhai ; Xiaoyun Guo ; Sahar Abubucker ; Chih-Wei Ko ; Cristiana Giancarlo ; Bradley Niesner ; Martino Alfredo Cappelluti ; Matteo Conti ; Lorena Donnici ; Pietro Spinelli ; Taesun Eom ; Mary S Morrison ; Ari E Friedland ; Raffaele De Francesco ; Angelo Lombardo ; Vic E Myer ; Aron B Jaffe ; Melissa Bonner ; Jennifer L MarloweSeries Type : Methylation profiling by high throughput sequencingOrganism : Hepatitis B virus ; Homo sapiens ; Mus musculusApproved chronic hepatitis B (CHB) therapies rarely result in functional cure, as they fail to permanently silence all transcriptionally active hepatitis B virus (HBV) DNA. CRMA-1001 employs an optimized epigenetic silencer that represses viral transcription through targeted deposition of DNA methylation on episomal and integrated HBV DNAs. In HBV mouse models, a single dose of CRMA-1001 produced >3 log10 reductions in viral biomarkers, which correlated with de novo methylation of HBV DNA. Three doses resulted in up to 90% of animals with undetectable hepatitis B surface antigen (HBsAg) and HBV DNA by 6 months post-treatment. In non-human primates, CRMA-1001 induced transient liver transaminase elevations only at the highest dose tested. Expression and DNA methylation profiling revealed no detectable unintended targets in the human genome. These findings support the initiation of clinical development of CRMA-1001 as a finite treatment course with the potential for functional cure in individuals living with CHB.
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💡 该来源还有 13 条内容，详见 文末

• GSE319072 开发一种优化的表观遗传沉默剂以转录失活慢性乙型肝炎中的病毒DNA [NHPAmpliconBisulfiteseq]
• GSE319071 开发一种优化的表观遗传沉默剂以转录失活慢性乙型肝炎中的病毒DNA [全基因组甲基化测序]
• GSE318266 开发一种优化的表观遗传沉默剂以转录失活慢性乙型肝炎中的病毒DNA
• GSE318226 开发一种优化的表观遗传沉默剂以转录失活慢性乙型肝炎中的病毒DNA [HybridCaptureMethylseq]
• GSE336489 全长层粘连蛋白332处理对表达或缺乏整合素α3β1的小鼠角质形成细胞转录组的影响
• GSE336418 DNMT3B 与 SMARCB1 发挥拮抗作用，是横纹肌样瘤的可靶向脆弱点 [甲基化阵列]
• GSE330343 组氨酸被谷氨酰胺取代，这一受调控的过程影响细胞存活，并提示癌症中组氨酸缺乏。
• GSE330016 单培养和三培养小胶质细胞的批量 RNA 测序
• GSE312649 微生物挥发性有机化合物 2,5-D 通过激活硝酸盐和铵盐转运促进拟南芥生长
• GSE318625 HSC-3口腔鳞状细胞癌细胞与坏死细胞共培养的基因表达谱分析
• GSE300218 胶质母细胞瘤中广泛的 DNA 损伤导致持续的染色质改变和基因表达重编程 [RNA-Seq]
• GSE291018 人小肠类器官（hSIOs）转录组分析（来自PiMM和PiZZ患者）
• GSE291017 突变型 Z α1-抗胰蛋白酶的积累会损害小鼠的肠道功能