详细内容（前10条）

1. ⭐ GSE300414 空间转录组学揭示头颈癌的分子肿瘤出芽特征

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、cancer、spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributor : Iordanis OurailidisSeries Type : OtherOrganism : Homo sapiens ; synthetic constructTumor budding is a histopathological feature associated with poor prognosis across multiple cancer types, including head and neck squamous cell carcinoma (HNSCC). Tumor buds represent the earliest traceable local invasion and are considered the origin of minimal residual disease, local recurrence, and metastasis. However, the molecular features underlying this phenomenon in HNSCC remain only partially characterized due to challenges in isolating tumor buds while preserving spatial context. Here, we employed high-plex spatial transcriptomics to specifically isolate and characterize tumor buds, complemented by single-cell RNA sequencing and pharmacogenomic analyses to comprehensively characterize the transcriptional landscape of tumor budding in human papillomavirus (HPV)-negative HNSCC. Our unprecedented spatial resolution revealed that tumor buds exhibited distinct gene expression profiles compared to tumor bulk, with significant upregulation of epithelial-mesenchymal transition (EMT) markers, extracellular matrix remodeling genes (including fibronectin and laminin-332 subunits), and coagulation pathway components. Unlike previous bulk tissue analyses, our approach enabled differential correlation analysis that uncovered extensive gene network rewiring both within tumor cells and between tumor and stromal compartments, highlighting dynamic molecular reprogramming during the budding process. We developed a novel 28-gene tumor budding signature (TBS) that effectively distinguished tumor buds from other compartments (AUC=0.97) and demonstrated independent prognostic value in the TCGA-HNSC cohort (HR=1.54, p=0.02), representing the first molecularly defined biomarker for tumor budding applicable to conventional transcriptomic data in HNSCC. Analyses of single-cell RNA-seq datasets confirmed the tumor-specific expression of the TBS, its association with a hybrid epithelial-mesenchymal state, its expression predominantly at the leading edges of tumors, and its induction via subtypes of epidermal growth factor receptor activities. Uniquely, our pharmacogenomic analysis revealed that SCC cell lines with high TBS scores showed increased sensitivity to Raf-MEK inhibitors, suggesting clinically actionable therapeutic vulnerabilities, which was confirmed in a 3D model of early local invasion. This integrated spatial-molecular approach provides novel insights into tumor bud…
• 🔗 查看原文

2. ⭐ GSE311383 利用 VisiumHD 对人肝脏进行高分辨率空间转录组学分析

• ✍️ 作者：未知作者
• 🏷️ 关键词：spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributors : Faizan Hasan ; Rachel D Edgar ; Gary D Bader ; Sonya A MacParlandSeries Type : OtherOrganism : Homo sapiensThe liver plays a critical role in metabolism and immune function. These crucial functions are diminished in chronic liver diseases, leading to over two million deaths annually worldwide due to liver failure. Single-cell transcriptomics has provided insights into the cellular composition of the liver in health and disease, but is inherently biased due to cell type-specific enrichment and destruction during the single-cell dissociation process. Previous work has highlighted difficulties in capturing specific populations such as cholangiocytes and hepatocytes. Spatial transcriptomics is a promising approach that does not have inherent bias for cell populations and adds important spatial context. Until recently, spatial transcriptomics technologies have only been at a multi-cellular resolution leading to mixed signals from different cell types. The latest spatial transcriptomic technology from 10X Genomics, VisiumHD, enables high-resolution spatial mapping of gene expression in tissue samples, offering a sophisticated platform for exploring the cellular composition of the liver. With a bin width of 2um, it can quantify transcripts at a sub-cellular resolution. Samples from three healthy human liver donors were sequenced and cells were clustered into cell types by integrating spatial transcriptomic data with existing single-cell reference maps. Spatially distinct cell signatures were identified through differential expression analyses and a high-resolution map of the liver was created. This resource provides cell-level and spatially-resolved insights into the cellular and geographical heterogeneity of the liver to serve as a resource for researchers to identify disease-specific spatial signatures and novel therapeutic targets.
• 🔗 查看原文

3. ⭐ GSE288114 Krüppel 样因子 2 控制早期耗竭的 T 细胞状态并抑制抗病毒免疫 [RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：immunity、T cell、RNA-seq
• 📝 描述：Contributors : Shengjun Geng ; Zifeng Li ; Hongling HuangSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusA key challenge in improving T cell-mediated immunotherapies is defining the factors that regulate functional versus exhaustion T cell fates. Through multi-round in vivo CRISPR screens in chronic LCMV Clone 13 infection and transcription factor (TF) benchmarking, we identified KLF2 as a top TF driving CX3CR1⁺ effector-like exhausted cell (Texeff-like) differentiation. Overexpression of KLF2 converted CX3CR1⁻ cells into Texeff-like cells by direct engagement of key loci. Conversely, loss of KLF2 increased inhibitory receptor expression and redirected cells toward terminal exhaustion. However, early after infection, KLF2 deficiency yielded increased CD8+ T cell accumulation and improved viral control. This effect was, in part, mediated by TOX and improved T cell localization with dendritic cells. Additional deletion of PD-1 further enhanced viral control, but induced severe immunopathology. Collectively, these findings identify KLF2 as a central regulator of the Texeff-like program and underscore exhaustion features as checkpoints balancing antiviral immunity and immunopathology.
• 🔗 查看原文

4. ⭐ GSE288039 Krüppel 样因子 2 控制早期耗竭的 T 细胞状态并抑制抗病毒免疫 [ATAC-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：immunity、T cell、ATAC-seq
• 📝 描述：Contributors : Shengjun Geng ; Zifeng Li ; Hongling HuangSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusA key challenge in improving T cell-mediated immunotherapies is defining the factors that regulate functional versus exhaustion T cell fates. Through multi-round in vivo CRISPR screens in chronic LCMV Clone 13 infection and transcription factor (TF) benchmarking, we identified KLF2 as a top TF driving CX3CR1⁺ effector-like exhausted cell (Texeff-like) differentiation. Overexpression of KLF2 converted CX3CR1⁻ cells into Texeff-like cells by direct engagement of key loci. Conversely, loss of KLF2 increased inhibitory receptor expression and redirected cells toward terminal exhaustion. However, early after infection, KLF2 deficiency yielded increased CD8+ T cell accumulation and improved viral control. This effect was, in part, mediated by TOX and improved T cell localization with dendritic cells. Additional deletion of PD-1 further enhanced viral control, but induced severe immunopathology. Collectively, these findings identify KLF2 as a central regulator of the Texeff-like program and underscore exhaustion features as checkpoints balancing antiviral immunity and immunopathology.
• 🔗 查看原文

5. GSE328390 阻断β肾上腺素能受体信号传导会加剧冠状病毒感染引起的炎症反应，并伴有趋化因子表达异常

• ✍️ 作者：未知作者
• 🏷️ 关键词：chemokine、inflammation
• 📝 描述：Contributor : jiangyating wuSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusHigh levels of catecholamines and the usage of β-adrenergic receptor (β-AR) blockers have been associated with adverse outcomes in COVID-19. This study aims to elucidate the underlying mechanisms and identify potential therapeutic targets.
• 🔗 查看原文

6. GSE327649 TET2突变克隆造血可防止T细胞耗竭并抑制癌症转移[scRNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、scRNA
• 📝 描述：Contributors : Tran B Nguyen ; Ai-Nhan T Le ; Mamiko Sakata-Yanagimoto ; Robert J VannerSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Mus musculusTET2-mutant clonal hematopoiesis (CH) is associated with reduced cancer metastasis in human cohorts. Using mouse models of colorectal cancer liver metastasis, we demonstrate that Tet2-deficient hematopoietic cells suppress metastatic tumor burden by preventing CD8+ T-cell exhaustion. Single-cell RNA-seq with paired V(D)J T-cell receptor (TCR) sequencing of CD45+ tumor-infiltrating leukocytes from Vav1CreTet2KO and Tet2fl/fl mice was performed to characterize transcriptional and clonotypic changes associated with TET2 loss in tumor-infiltrating immune cells.
• 🔗 查看原文

7. GSE327454 TET2 突变克隆造血可防止 T 细胞耗竭并抑制癌症转移 [RNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、RNA-seq
• 📝 描述：Contributors : Tran B Nguyen ; Ai-Nhan T Le ; Mamiko Sakata-Yanagimoto ; Robert J VannerSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusTET2-mutant clonal hematopoiesis (CH) is associated with reduced cancer metastasis in human cohorts. Using mouse models of colorectal cancer liver metastasis, we demonstrate that Tet2-deficient hematopoietic cells suppress metastatic tumor burden by preventing CD8+ T-cell exhaustion. Bulk RNA-seq of sorted CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) from Vav1CreTet2KO, Cd4CreTet2KO, and Tet2fl/fl control mice was performed to characterize transcriptional changes associated with Tet2 loss in tumor-infiltrating T cells.
• 🔗 查看原文

8. GSE327666 BPTF 对疫苗诱导的生发中心 B 细胞反应至关重要

• ✍️ 作者：未知作者
• 🏷️ 关键词：vaccine、B cell
• 📝 描述：Contributors : Alexandria J Sturtz ; Birk Evavold ; Zarifeh H Rarani ; Wafaa Alsoussi ; Julian Q Zhou ; Hanover Matz ; Hiromi Muramatsu ; Wren Simkins ; Sameer Kumar Malladi ; Katherine McIntire ; Jishnu Das ; Jackson S Turner ; Norbert Pardi ; Ali H EllebedySeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusGerminal centers (GCs) are microanatomical structures in which antigen-specific B cells undergo proliferation, somatic hypermutation, and affinity-based competition to select high affinity clones that differentiate into memory B cells (MBCs) and plasma cells (PCs). B cell progression through the GC is tightly regulated and the molecular determinants that modulate GC B cell proliferation and survival are still under investigation. Here, we use a conditional deletion mouse model to demonstrate that bromodomain PHD finger transcription factor (BPTF), a subunit of the nucleosome remodeling factor (NURF) chromatin remodeling complex, is required for robust GC B cell responses following vaccination. In GC B cells, Bptf loss induces a stress-like transcriptional profile and a shift towards PC identity-defining transcriptional programing, although this does not lead to accumulation of functional PCs. Rather, we show that BPTF-deficient GC B cells are prone to cell death. Cumulatively, our data demonstrate that BPTF is necessary for GC B cell maintenance and robust antigen-specific B cell responses.
• 🔗 查看原文

9. GSE327270 索马鲁肽在 HIV 相关脂肪增生的随机试验中减缓表观遗传衰老

• ✍️ 作者：未知作者
• 🏷️ 关键词：aging、epigenetic
• 📝 描述：Contributor : Michael J CorleySeries Type : Methylation profiling by genome tiling arrayOrganism : Homo sapiensGenome-wide DNA methylation profiling of PBMC samples from people living with HIVHIV-1 infection impacts biological aging, and epigenetic clocks highlight epigenetic age acceleration in people with HIV. Despite evidence indicating Glucagon-like peptide-1 receptor agonist in beneficial HIV-associated cardiometabolic outcomes, effects on aging biomarkers in HIV epigenetic studies is a major gap in knowledge. Hence, we generated a representative epigenetic dataset to examine Glucagon-like peptide-1 receptor agonist in epigenetic ageing and relationships to clinical phenotypes.
• 🔗 查看原文

10. GSE320433 卵巢癌模型中的顺铂耐药性是由微管动力学调节因子TPPP3介导的，TPPP3与微管蛋白密码重连协同作用

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、resistance
• 📝 描述：Contributors : Sachi Horibata ; Kishore K Mahalingan ; Ruchi Patel ; Yu Fan ; Jordan M Hotz ; Adriana Ponton-Almodovar ; Keith MacRenaris ; Yan Li ; Daoud Meerzaman ; Michael M Gottesman ; Antonina Roll-MecakSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensCisplatin is a mainstay in cancer treatment, but toxicity and resistance limit its potential. Using RNA-seq, we show that ovarian cancer cells undergo broad changes in the microtubule cytoskeleton that correlate with resistance. Consistent with this, we find that cisplatin directly impacts microtubule dynamics in vitro and in cells. Paclitaxel counteracts cisplatin and increases resistance. By purifying tubulin from cisplatin sensitive resistant and re-sensitized ovarian cancer cells, we demonstrate that resistance acquisition rewires the tubulin code leading to microtubule stabilization. Furthermore, tubulin polymerization promoting protein 3 (TPPP3) contributes to resistance. In vitro, TPPP3 synergizes with tubulin isotypes from resistant cells to yield maximal microtubule stabilization in response to cisplatin. Database analysis shows that patients with low TPPP3 levels have improved therapeutic outcome. Our findings implicate TPPP3 and microtubule dysregulation in cisplatin resistance, independent of effects through DNA damage, and have bearing on the etiology of cisplatin-associated neuropathies and ototoxicity.
• 🔗 查看原文

💡 该来源还有 22 条内容，详见 文末

详细内容（全部2条）

1. ⭐ 科学家发现细菌可以通过“爆炸”传播抗生素耐药性。

• ✍️ 作者：未知作者
• 🏷️ 关键词：bacteria、regex:bacter(ia|ial|ium)、resistance
• 📝 描述：Scientists have uncovered a surprising twist in how bacteria share genes—including those that spread antibiotic resistance. Tiny virus-like particles called gene transfer agents (GTAs), once ancient viral invaders, have been repurposed by bacteria into delivery systems that shuttle DNA between neighboring cells. The study reveals a key control hub of three genes, dubbed LypABC, that triggers bacterial cells to burst open and release these DNA-packed couriers.
• 🔗 查看原文

2. 美国食品药品监督管理局 (FDA) 最新建议支持基于下一代测序技术对个性化基因疗法中的脱靶编辑进行安全性评估。

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing
• 📝 描述：FDA draft guidance highlights next-generation sequencing approaches for evaluating off-target effects and genomic integrity in genome editing therapies, supporting safer gene therapy…
• 🔗 查看原文

• GSE288041 Krüppel 样因子 2 控制早期耗竭的 T 细胞状态并抑制抗病毒免疫 [TCR-Seq]
• GSE327756 TET2突变克隆造血可防止T细胞耗竭并抑制癌症转移
• GSE325029 METTL3 调控 HCC1143 和 MDA-MB-231 三阴性乳腺癌细胞系的细胞活力和迁移能力
• GSE315844 EBNA1 抑制剂揭示 CDC7 和 POU2F1 是 EBV 上皮癌的直接功能靶点 [ChIP-Seq]
• GSE290636 对接受抗逆转录病毒疗法且HIV病毒载量受到抑制的感染者在分析性治疗中断前采集的血液样本进行RNA测序分析
• GSE281938 牙龈卟啉单胞菌抑制呼吸道合胞病毒感染，同时抑制抗病毒免疫
• GSE328075 CD8⁺ T 细胞耗竭样和线粒体功能障碍定义了猫慢性龈口炎的免疫失调
• GSE326845 ASCL2 通过 FSAN 介导的 MDR1 棕榈酰化驱动索拉非尼耐药性
• GSE310096 血小板长链非编码RNA LUCAT1与重大不良心血管事件风险相关
• GSE310095 全血转录组学区分冠状动脉疾病和外周动脉疾病的循环基因表达
• GSE328029 MiT 融合、TSC1–TSC2 分歧和干细胞样程序揭示 PEComa 的不同起源和脆弱性 [甲基化]
• GSE328026 MiT融合、TSC1-TSC2分歧和干细胞样程序揭示PEComa的不同起源和脆弱性[RNA-seq]
• GSE327938 母源Polycomb印记通过低级甲基化状态在果蝇早期发育中得以维持
• GSE327937 MiT融合、TSC1-TSC2分歧和茎状程序揭示PEComa的不同起源和脆弱性[scRNA-seq]
• GSE327855 内皮细胞 FGF13 通过加速氧非依赖性 HIF-1α 降解来抑制血管生成 [RNA-Seq]
• GSE327840 RNA-seq 分析单核细胞、THP-1 细胞、成纤维细胞、平滑肌细胞和内皮细胞的 LPS 耐受性
• GSE327820 转录组分析揭示了蓝莓果实发育过程中角质蜡（霜）形成的分子机制。
• GSE296044 源自恶性疟原虫感染红细胞的细胞外囊泡转移 miR451a，破坏中性粒细胞功能并导致免疫失调
• GSE295211 RNA-Seq 和 BiFC 联合分析表明，NtCISZOG 调控 NtChlH 的表达，并正向调控烟草中的叶绿素含量。
• GSE295027 双作用转录调节因子 Cas5 对钙稳态和致病性的协调调控 [RNA-Seq]
• GSE295026 双重作用转录调节因子 Cas5 对钙稳态和致病性的协同调控 [ChIP-Seq]
• GSE264314 局部应用尿石素A可延缓皮肤内在老化并保护皮肤免受UVB介导的光损伤：随机临床试验结果