详细内容（前10条）

1. ⭐ GSE294006 缺氧影响转移性透明细胞肾细胞癌的治疗反应和耐药性 [空间转录组学]

• ✍️ 作者：未知作者
• 🏷️ 关键词：carcinoma、resistance、spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributors : Lynda Vuong ; Fengshen Kuo ; Abraham A HakimiSeries Type : OtherOrganism : Homo sapiensVascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors (VEGFR-TKIs) and aPD1 combinations are effective in multiple solid tumors, particularly in clear cell renal cell carcinoma (ccRCC), due it’s characteristic pseudo-hypoxic, hyper-angiogenic state driven by biallelic VHL-loss. However, long-term durability is inferior to dual aPD1/aCTLA4 regimens, yet the mechanisms underlying these differences remain unclear. Since tumor-associated macrophages (TAMs) are implicated in therapeutic resistance, we used scRNAseq to investigate TAM evolution following VEGFR-TKI, aPD1 and combined VEGFR-TKI/aPD1 treatment in a transgenic ccRCC mouse model. We identify hypoxia-responsive SPP1+ TAMs that are absent in baseline pseudo-hypoxic tumors. This proxy of true hypoxia tracks with successful response to VEGFR-TKI/aPD1 in mouse and human on-treatment samples, reflecting treatment-induced hypoxic necrosis. Paradoxically, pretreatment hypoxia predicted worse outcomes across multiple VEGFR-TKI/aPD1 trial and real-world cohorts and extended exposure to hypoxia-inducing VEGFR-TKIs and aPD1 exacerbated metastasis in mice, highlighting the dual implications of hypoxia in ccRCC disease trajectory.
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2. ⭐ GSE289312 低输入量 RNA 测序表明肠道共生细菌形态异质性的潜在代谢特化

• ✍️ 作者：未知作者
• 🏷️ 关键词：regex:bacter(ia|ial|ium)、metabolic、RNA-seq、gut、regex:gut(-?microbiome)?
• 📝 描述：Contributors : Elise Bornet ; Gianluca Prezza ; Laura Cecchino ; Laura Jenniches ; Jochen Behrends ; Caroline Tawk ; Kerwyn Casey Huang ; Till Strowig ; Jorg Vogel ; Lars Barquist ; Antoine-Emmanuel Saliba ; Alexander J WestermannSeries Type : Expression profiling by high throughput sequencingOrganism : Bacteroides thetaiotaomicronIsogenic bacteria can be phenotypically diverse. This heterogeneity is evident in the Bacteroidota, a predominant phylum of the human gut microbiota. These bacteria adopt diverse morphologies, yet the molecular basis of their morphological heterogeneity is poorly understood. Here, we systematically characterize the variation in cellular morphology of Bacteroides thetaiotaomicron cells during laboratory growth and after isolation from different host niches. We develop a sensitive transcriptomics approach and apply it to B. thetaiotaomicron sorted into sub-populations of varying cell sizes. Differential expression analysis indicates metabolic specialization associated with morphology. Transcriptomic data also reveal morphological marker genes, whose size-dependent expression is validated through fluorescence in situ hybridization. Morphological characterization of deletion and overexpression mutants reveals that specific marker genes causally contribute to B. thetaiotaomicron cell-size determination. Since phenotypic heterogeneity is a common feature of microbial consortia, this study serves as a blueprint for understanding the role of bacterial genes in morphological variation
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3. ⭐ GSE328849 空间转录组学鉴定 IL-32 为与人类糖尿病肾病肾小管损伤相关的脂滴相关细胞因子 [GeoMx]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cytokine、spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributors : Kieran Meadows ; Hyunjae Chung ; Son Vo ; Aysa Imanzadeh ; Heewon Seo ; Sisay G Belay ; Asha Swamy ; Wulin Teo ; Kevin Chapman ; Graciela Andonegui ; Hallgrimur Benediktsson ; Peter K Stys ; Thang Pham ; Daniel A Muruve ; Justin ChunSeries Type : OtherOrganism : Homo sapiensDiabetic kidney disease (DKD) is a severe complication of diabetes mellitus and the leading cause of chronic kidney disease worldwide. Among the many drivers of tubular injury, lipid accumulation and inflammation are emerging as major contributors to kidney disease progression, but the molecular link between lipid metabolism and inflammatory signaling remains to be determined. Kidney biopsies from patients with DKD across pathologic classes were labelled for lipid droplets and analyzed by Nile Red spectroscopy. Digital spatial profiling and single-cell spatial transcriptomics were performed on samples from 14 patients representing different DKD classes. RNA scope and immunofluorescence microscopy were used for data validation and characterization. Lipid droplets (LD) were increasingly abundant in advanced stages of DKD, primarily accumulating in the proximal tubules. Single-cell spatial transcriptomics identified several genes—DUSP5, AZU1, COL9A1, HSPB1, and IGFBP7—as highly upregulated in DKD. Remarkably, IL32, which encodes a LD-associated cytokine, was highly enriched in injured proximal tubules. Immunofluorescence confirmed IL-32 localization to LDs predominantly within KIM1 positive tubules in moderate to advanced DKD. Furthermore, injured IL-32 expressing tubules were in close proximity to infiltrating neutrophils and macrophages, immune effectors of non-resolving inflammation and kidney disease progression. IL-32 is a LD-associated cytokine upregulated during tubular injury that represents a potential link between lipid dysregulation, inflammation and progression in human DKD.
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4. ⭐ GSE305486 ATF7ip 通过促进终末 CD8+ T 细胞耗竭 III 抑制肿瘤免疫反应

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、immune、T cell
• 📝 描述：Contributors : Sujit Kashyap ; Jun Hyung Sin ; Michael R WaterfieldSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusCD8+ T cell exhaustion limits the immune response to tumors because of ineffective T cell effector functions. Thus, therapies that inhibit T-cell exhaustion are critical for optimizing cancer treatment. Recent studies have implicated epigenetic proteins in T-cell exhaustion. Here, we identified activating transcription factor 7 interacting protein (ATF7ip) as an epigenetic protein critical for inducing T cell exhaustion. Loss of Atf7ip in CD8+ T cells results in decreased terminal exhaustion and increased numbers of progenitor-exhausted cells in both chronic viral infections and cancer. Owing to decreased exhaustion, Atf7ip-deficiency in CD8+ T cells leads to an enhanced immune response to tumors. Mechanistically, ATF7ip functions to stimulate the deposition of repressive H3K9me3 at critical immune-effector gene loci, such as Il7r and Il2 leading to enhanced exhaustion. Our data suggest that ATF7ip may be a rational target for deletion in adoptive T-cell therapies to reduce CD8+ T-cell exhaustion.
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5. ⭐ GSE305418 ATF7ip 通过促进终末 CD8+ T 细胞耗竭 II 抑制肿瘤免疫反应

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、immune、T cell
• 📝 描述：Contributors : Sujit Kashyap ; Jun Hyung Sin ; Michael R WaterfieldSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusCD8+ T cell exhaustion limits the immune response to tumors because of ineffective T cell effector functions. Thus, therapies that inhibit T-cell exhaustion are critical for optimizing cancer treatment. Recent studies have implicated epigenetic proteins in T-cell exhaustion. Here, we identified activating transcription factor 7 interacting protein (ATF7ip) as an epigenetic protein critical for inducing T cell exhaustion. Loss of Atf7ip in CD8+ T cells results in decreased terminal exhaustion and increased numbers of progenitor-exhausted cells in both chronic viral infections and cancer. Owing to decreased exhaustion, Atf7ip-deficiency in CD8+ T cells leads to an enhanced immune response to tumors. Mechanistically, ATF7ip functions to stimulate the deposition of repressive H3K9me3 at critical immune-effector gene loci, such as Il7r and Il2 leading to enhanced exhaustion. Our data suggest that ATF7ip may be a rational target for deletion in adoptive T-cell therapies to reduce CD8+ T-cell exhaustion.
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6. ⭐ GSE293952 缺氧影响转移性透明细胞肾细胞癌的治疗反应和耐药性 [bulk RNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：carcinoma、resistance、RNA-seq
• 📝 描述：Contributors : Lynda Vuong ; Fengshen Kuo ; Abraham A HakimiSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensVascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors (VEGFR-TKIs) and aPD1 combinations are effective in multiple solid tumors, particularly in clear cell renal cell carcinoma (ccRCC), due it’s characteristic pseudo-hypoxic, hyper-angiogenic state driven by biallelic VHL-loss. However, long-term durability is inferior to dual aPD1/aCTLA4 regimens, yet the mechanisms underlying these differences remain unclear. Since tumor-associated macrophages (TAMs) are implicated in therapeutic resistance, we used scRNAseq to investigate TAM evolution following VEGFR-TKI, aPD1 and combined VEGFR-TKI/aPD1 treatment in a transgenic ccRCC mouse model. We identify hypoxia-responsive SPP1+ TAMs that are absent in baseline pseudo-hypoxic tumors. This proxy of true hypoxia tracks with successful response to VEGFR-TKI/aPD1 in mouse and human on-treatment samples, reflecting treatment-induced hypoxic necrosis. Paradoxically, pretreatment hypoxia predicted worse outcomes across multiple VEGFR-TKI/aPD1 trial and real-world cohorts and extended exposure to hypoxia-inducing VEGFR-TKIs and aPD1 exacerbated metastasis in mice, highlighting the dual implications of hypoxia in ccRCC disease trajectory.
• 🔗 查看原文

7. ⭐ GSE266290 整合表观遗传学、蛋白质组学和代谢组学揭示Wnt/β-catenin信号通路在冬凌草甲素诱导的生殖毒性中的作用

• ✍️ 作者：未知作者
• 🏷️ 关键词：metabolomics、proteomics、pathway
• 📝 描述：Contributors : Qibin Wu ; Xinyue Gao ; Yifan Lin ; Caijin WuSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Homo sapiensOridonin is the primary active ingredient in traditional Chinese medicine Rabdosia rubescens, displaying various pharmacological activities such as anti-inflammatory, anti-tumor, and antibacterial effects. It is widely used in the clinical treatment of acute and chronic pharyngitis, tonsillitis, and bronchitis. Nevertheless, the reproductive toxicity of oridonin significantly restricts its clinical application, with the exact mechanism remaining unclear. This study aimed to investigate the mechanism of oridonin-induced damage to HTR-8/SVneo cells. By integrating epigenetics, proteomics, and metabolomics approaches, the mechanisms of oridonin-induced reproductive toxicity were discovered and confirmed through fluorescence imaging, RT-qPCR, and Western blotting. Experimental findings indicated that oridonin altered m6A levels, gene and protein expression levels, along with metabolite levels within the cells. Additionally, oridonin triggered oxidative stress and mitochondrial damage, leading to a notable decrease in WNT6, β-catenin, CLAUDIN-1, and ZO-1 protein levels. This implies that the inhibition of the Wnt/β-catenin pathway and disruption of tight junctions may be attributed to the cytotoxicity induced by oridonin and mitochondrial dysfunction, ultimately resulting in damage to HTR-8/SVneo cells.
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8. ⭐ GSE328930 DUTRENEO试验：基于生物标志物的前瞻性批量治疗选择和肌层浸润性膀胱癌免疫治疗反应的空间转录组学分析

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、regex:immuno(logy|therapy|suppression)、spatial
• 📝 描述：Contributors : Francisco X Real ; Mustafa Sibai ; Eduard Porta-Pardo ; Enrique Grande ; Jaime Martinez de VillarrealSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensPredictive biomarkers for immune checkpoint inhibitors (ICI) have largely been identified retrospectively, but their clinical utility remains unproven in prospective settings. Here, we report the results of DUTRENEO, a prospective, randomized phase 2 trial testing whether a retrospective, well-validated, 18-gene tumor inflammation signature (TIS) could guide neoadjuvant ICI therapy in muscle-invasive bladder cancer. The trial failed to meet its primary endpoint, demonstrating that bulk gene expression stratification does not sufficiently enrich for responders in this setting. To understand the biological determinants of this failure, we generated a single-cell spatial transcriptomics dataset profiling 377 genes in ~5.4 million cells across large tissue areas. This high-resolution profiling revealed that response to ICI is governed by spatial architectures invisible to bulk assays, specifically the proximity of CD8⁺ T cells to cancer cells and the localized co-expression of checkpoints within epithelial-rich neighborhoods. Furthermore, we identified fibroblast-rich communities as a key feature of immune exclusion in non-responders. We derived a quantitative framework for the design of future clinical trials incorporating spatial analyses, demonstrating that reducing the annotation panel to ≥77 genes and sampling ≥3 mm tissue diameter preserves predictive spatial signal while enabling scalable throughput. These findings elucidate the architectural constraints that limit bulk biomarkers and provide a quantitative framework to embed spatial profiling into clinical studies.
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9. GSE320046 HNF4a 控制 IMA 的生长、特性和对 KRAS 抑制的反应 [ATAC-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：ATAC-seq、KRAS
• 📝 描述：Contributors : Headtlove Essel Dadzie ; Eric L SnyderSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusCellular plasticity is a key feature of cancer that enables tumor cells to switch lineage identities, driving disease progression and resistance to therapy. In invasive mucinous adenocarcinoma (IMA), a pronounced pulmonary-to-gastric lineage switch occurs as NKX2.1 is lost and HNF4α, a master regulator of gastric differentiation, is upregulated. Although absent in normal alveolar type 2 cells, HNF4α is aberrantly expressed in most IMA tumors. In this study, we investigate the role of HNF4α within established IMAs and find that it directly activates a gastric differentiation program, particularly in pit cells. Loss of HNF4α disrupts this program and permits FOXA1 and FOXA2 to bind new regulatory sites, leading to the upregulation of neuronal and liver-like gene modules. In light of the poor response of mucinous tumors to KRAS inhibitors, we investigated whether HNF4α modulates sensitivity to KRASG12D targeted therapy. Treatment with MRTX1133 revealed that loss of HNF4α significantly increases IMA sensitivity by reducing the IC50 in vitro and enhancing tumor regression in vivo. Mechanistically, HNF4α deletion impairs cell-cycle progression in drug-tolerant persister cells, while tumors retaining HNF4α maintain these cell-cycle regulators despite KRAS inhibition, promoting persister cell survival. Our findings establish HNF4α as a critical driver of IMA biology governing both gastric differentiation and resistance to KRAS inhibitors and support the development of combination strategies to overcome therapeutic resistance in IMA.
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10. GSE294571 HNF4a 控制 IMA 的生长、特性和对 KRAS 抑制的反应 [scRNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：scRNA、KRAS
• 📝 描述：Contributors : Headtlove Essel Dadzie ; Eric L SnyderSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusCellular plasticity is a key feature of cancer that enables tumor cells to switch lineage identities, driving disease progression and resistance to therapy. In invasive mucinous adenocarcinoma (IMA), a pronounced pulmonary-to-gastric lineage switch occurs as NKX2.1 is lost and HNF4α, a master regulator of gastric differentiation, is upregulated. Although absent in normal alveolar type 2 cells, HNF4α is aberrantly expressed in most IMA tumors. In this study, we investigate the role of HNF4α within established IMAs and find that it directly activates a gastric differentiation program, particularly in pit cells. Loss of HNF4α disrupts this program and permits FOXA1 and FOXA2 to bind new regulatory sites, leading to the upregulation of neuronal and liver-like gene modules. In light of the poor response of mucinous tumors to KRAS inhibitors, we investigated whether HNF4α modulates sensitivity to KRASG12D targeted therapy. Treatment with MRTX1133 revealed that loss of HNF4α significantly increases IMA sensitivity by reducing the IC50 in vitro and enhancing tumor regression in vivo. Mechanistically, HNF4α deletion impairs cell-cycle progression in drug-tolerant persister cells, while tumors retaining HNF4α maintain these cell-cycle regulators despite KRAS inhibition, promoting persister cell survival. Our findings establish HNF4α as a critical driver of IMA biology governing both gastric differentiation and resistance to KRAS inhibitors and support the development of combination strategies to overcome therapeutic resistance in IMA.
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详细内容（全部2条）

1. FIRST-seq——一种基于纳米孔的cDNA测序平台，用于RNA修饰和结构分析

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing
• 📝 描述：RNA sequencing using nanopore technology enables detection of RNA modifications and structure at single-nucleotide resolution through reverse transcription error signatures…
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2. 长读长RNA测序和多聚核糖体谱分析框架揭示了转座元件驱动的转录本多样性

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing
• 📝 描述：RNA sequencing reveals how transposable elements drive alternative splicing and alter translation in glioblastoma, generating diverse RNA isoforms linked to cancer progression…
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• GSE294570 HNF4a 控制 IMA 的生长、特性和对 KRAS 抑制的反应 [bulk RNAseq]
• GSE294109 低氧影响转移性透明细胞肾细胞癌的治疗反应和耐药性 [scRNAseq]
• GSE293450 Hypoxia shapes both therapeutic response and resistance in metastatic clear cell renal cell carcinoma
• GSE264442 表观遗传调控因子反复突变引发的凝聚作用促进癌症发生
• GSE328669 用于组织中基于T细胞受体可变基因的克隆型分析的空间原位杂交平台
• GSE295724 神经元微外显子通过斑马鱼的 cAMP-PKA-CREB ​​通路调节觉醒
• GSE325162 肠道菌群调节的谷氨酸可恢复因高龄生育而下降的卵母细胞质量
• GSE294619 eIF4G2介导的组蛋白修饰酶翻译起始对于肠道干细胞的维持和分化至关重要
• GSE328831 肺结节病FFPE肺组织中激光显微切割的肉芽肿及其邻近非肉芽肿区域的批量RNA测序
• GSE327580 IDH突变型胶质瘤进展中的遗传和细胞状态变化[snATAC]
• GSE326221 IDH突变型胶质瘤进展过程中获得的遗传和细胞状态变化[snRNA-seq]
• GSE326070 白细胞介素-34 诱导的 Arg1+ 巨噬细胞在乳腺癌脑转移中起关键作用。
• GSE325996 白细胞介素-34诱导的Arg1+巨噬细胞在乳腺癌脑转移中发挥关键作用
• GSE324860 IDH突变型胶质瘤进展过程中获得的遗传和细胞状态变化[类器官]
• GSE295557 First-in-Class CAR T Cell Therapy Selectively Eliminates Mutant Calreticulin-Driven Malignancies in a Fibrotic Niche
• GSE294573 HNF4a 控制 IMA 的生长、特性和对 KRAS 抑制的反应。
• GSE328709 I型干扰素信号在小胶质细胞中驱动创伤性脑损伤后的突触吞噬和神经元丢失
• GSE324146 H3多巴胺化和CaMKII调节弥漫性中线胶质瘤对CDK9抑制剂的反应
• GSE302647 有丝分裂起始过程中组蛋白修饰的时间分辨图谱
• GSE297044 SETD2 缺陷导致线粒体 DNA 泄漏，并在透明细胞肾细胞癌中产生对 BCL-XL 的可药物依赖性
• GSE294572 HNF4a 控制 IMA 的生长、特性和对 KRAS 抑制的反应 [ChIP- seq]
• GSE290144 Runx1 缺陷揭示胸腺肺泡 II 型上皮模拟细胞 [scRNA-seq]
• GSE285400 抗原特异性B细胞在可溶性或颗粒性抗原刺激后的转录组
• GSE328517 比较用 AdV-Fe3O4@PACM 和 AdV-iCD47-Fe3O4@PACM 治疗的小鼠肿瘤组织中 TAM 基因表达的差异。
• GSE328399 中性粒细胞胞外陷阱通过促进免疫微血栓形成加重 COVID-19 相关急性黄斑神经视网膜病变
• GSE295555 Numb-Ifi204 抑制 LPS 诱导的小胶质细胞活化和海马炎症。
• GSE280280 BRAF突变型结直肠癌中MAPK抑制反应期间ETS和MYC核心调控回路介导的细胞可塑性重编程
• GSE280266 BRAF突变型结直肠癌中MAPK抑制反应期间通过ETS和MYC核心调控回路重编程细胞可塑性。
• GSE277487：小鼠皮层在CCI诱导的创伤性脑损伤后多个时间点的单核RNA测序
• GSE261933 KMT2F 组蛋白甲基转移酶与 RNA 聚合酶 I 机制相互作用，促进核糖体 RNA 转录。