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1. ⭐ GSE329449 具有胆管细胞表型的肿瘤细胞在肝细胞癌中与成纤维细胞形成致癌微环境

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、carcinoma、regex:onco(logy|logist|gene|genic)
• 📝 描述：Contributors : Liwen Chiou ; Yulin Jhuang ; Zhongzhe Lin ; Chingyao Yang ; Yungming JengSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBackground: A subset of hepatocellular carcinoma (HCC) exhibits cholangiocytic features associated with aggressive behavior, poor prognosis, and treatment resistance, but the underlying mechanisms remain unclear. We investigated the characteristics of duct-like (DL) tumor cells and their interactions with fibroblasts in HCC. Methods: Single-cell RNA sequencing data from 40 primary HCC samples were integrated to identify tumor subpopulations and signaling networks. Spatial transcriptomic datasets were analyzed to assess colocalization of DL cells and fibroblasts. Functional studies were performed using liver cancer cell lines cultured on collagen I or treated with cancer-associated fibroblast (CAF)-conditioned medium, followed by molecular analyses. Results: A distinct DL tumor cell population expressing cholangiocytic and stem-like markers was identified. DL cells showed activation of Wnt, MAPK, Notch, and Hippo pathways, whereas non-duct-like cells retained hepatocytic metabolic programs. Fibroblasts preferentially interacted with DL cells through extracellular matrix ligands, especially collagens and fibronectin, binding integrins and syndecans. Spatial transcriptomics demonstrated close colocalization of DL cells and fibroblasts in regions with high oncogenic pathway activity. SPP1 emerged as a major mediator of DL-to-fibroblast signaling. In vitro, collagen I and CAF-conditioned medium promoted cholangiocytic features and suppressed hepatocytic differentiation. Conclusion: DL tumor cells form a reciprocal oncogenic niche with fibroblasts that promotes HCC progression and therapeutic resistance
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2. ⭐ GSE329229 利用空间转录组学分析高胆固醇饮食和酒精喂养的小鼠肝脏

• ✍️ 作者：未知作者
• 🏷️ 关键词：spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributors : Irina Tikhanovich ; Michael SchonfeldSeries Type : OtherOrganism : Mus musculusBackground & Aims: Alcohol-associated liver disease (ALD) heavily contributes to global alcohol related mortality. Alcohol can synergize with other causes of liver disease such as metabolic syndrome induced by western diet (high fat, high fructose, high cholesterol). However, the role of individual western diet components in ALD development is not fully understood. We aimed to study the role of cholesterol in alcohol pathogenesis. Previous studies have shown that hepatic cholesterol metabolism is dysregulated with alcohol use resulting in altered lipoprotein levels. We aimed to study the role of cholesterol in ALD development using a mouse model. Approach and results: 8-week-old male mice were fed ad libitum with low fat high cholesterol diet (Research Diets, cat# D24120501, 1% cholesterol) in combination with 20% EtOH in the drinking water for 10 weeks. Compared to high-cholesterol diet alone, alcohol treated mice showed elevated levels of serum ALT and AST, INR/PT, increased liver inflammation, fibrosis, ductular reaction and signs of liver failure such as reduced HNF4α and albumin production. To assess the mechanism of alcohol-induced pathology, we performed spatial transcriptomic analysis using 5k gene Xenium panel (10x Genomics). We found that the liver adapted to high cholesterol diet by increasing cholesterol metabolism in hepatocytes. In contrast, alcohol impaired liver adaptation to high cholesterol diet by reducing cholesterol metabolism, HDL production, and hepatic cholesterol secretion, thus driving inflammation and fibrosis. Hepatocyte specific Kdm5b knockout mice were partially protected from alcohol effects by restoring cholesterol secretion in part through an upregulation of Abcg8. Accordingly, these mice were protected against alcohol-induced fibrosis development and inflammation. Conclusion: In summary, alcohol impairs liver adaptation to high cholesterol diet. Increasing liver cholesterol secretion by KDM5B inhibition protects liver from ALD development.
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3. ⭐ GSE316305 髓系来源的WNTs会损害胰腺癌的抗肿瘤免疫反应

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、cancer、immune
• 📝 描述：Contributors : Na Hyun Kim ; Young Min Song ; San Sung Kwon ; Sang Hyub Lee ; Eun Na Kim ; Seung Hyeok Seok ; Yi Rang NaSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusWe performed single-cell RNA sequencing on tumor-infiltrating cells isolated from orthotopic KPC pancreatic tumors at day 21 post-implantation. The objective was to determine how macrophage-specific ablation of WNT secretion (Csf1r-Cre;Porcnfl/fl) reshapes the PDAC immune microenvironment.
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4. GSE313112 STC-15 对 METTL3 的抑制诱导 RNA 错误加工，导致 dsRNA 形成并激活先天免疫 [RNA-Seq MC38]

• ✍️ 作者：未知作者
• 🏷️ 关键词：immunity、RNA-seq
• 📝 描述：Contributor : Harry FischlSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe RNA methyltransferase METTL3 is responsible for the generation of m6A, the most abundant modification mark on mRNA and long non-coding RNA. Accumulating evidence suggests numerous roles of METTL3 in cancer initiation and progression and highlights the potential for targeting this enzyme in oncology. STC-15 is a potent and selective METTL3 inhibitor and the first RNA modifying enzyme inhibitor to enter human clinical development. It is structurally related to the previously published tool inhibitors STM2457 and STM3675. We previously identified the induction of a cancer cell-intrinsic interferon response following pharmacological inhibition of METTL3, leading to activation of T-cell-mediated anti-tumour response. Here, we profiled m6A levels at nucleotide resolution using GLORI and characterised RNA changes following METTL3 inhibition with STC-15 or STM3675. Following loss of m6A, we uncovered aberrant mRNA transcripts arising from intron retention (IR) and transcriptional run-on (RO) events downstream of m6A-enriched exons in human cancer cells and in tumour samples in vivo. We found that these IR and RO events produce double-stranded RNA and are bound by the cytoplasmic dsRNA sensor MDA5.Using preclinical in vitro and in vivo models, we characterised in detail the anti-tumour immune responses induced by STC-15. Our study reveals how METTL3 inhibition leads to dsRNA accumulation, which triggers a type I interferon response and induces anti-tumour immunity. Together, these findings provide a mechanistic rationale for STC-15 as a novel anti-cancer drug both as monotherapy and in combination with anti-PD1 checkpoint inhibitors.
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5. GSE319852 RXRα抑制驱动脓毒症中的肝脏代谢和免疫功能障碍：CLP/SHAM模型中的RXRα敲除。

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune、metabolic
• 📝 描述：Contributors : Matyas Jelinek ; Jolien Vandewalle ; Marah Heyerick ; Tineke Vanderhaeghen ; Céline Van Dender ; Steven Timmermans ; Madeleine Hellemans ; Daria Fijalkowska ; Martin Guilliams ; Karolien De Bosscher ; Claude LibertSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusSepsis is a life-threatening condition where a dysregulated host response to infection causes organ dysfunction and the collapse of metabolic and immune functions. Here, we identify hepatocyte Retinoid X Receptor α (RXRα) as a central integrator of host resilience during polymicrobial sepsis. We show that hepatic Rxra expression is transcriptionally dependent on the upstream regulator Hepatocyte Nuclear Factor 4 α (HNF4α), and that sepsis rapidly suppresses RXRα abundance at both the mRNA and protein levels. Transcriptomic profiling further reveals that the septic liver develops partial resistance to pharmacological RXR activation by its agonist Bexarotene (Bex). Despite this, prophylactic treatment with Bex preserves metabolic stability, enhances bacterial clearance, and improves survival. Using hepatocyte-specific inducible RXRα-deficient mice (RXRαiAlbKO), we demonstrate that this protective effect is strictly dependent on hepatocyte RXRα. Mechanistically, the loss of RXRα in hepatocytes leads to a profound reduction in the liver-resident macrophage, Kupffer cells (KC), resulting in uncontrolled bacterial dissemination and increased mortality. This defect is phenocopied by selective KC depletion. These findings establish that hepatocyte RXRα is essential for maintaining the hepatic macrophage niche, thereby linking hepatocellular transcriptional competence to systemic antibacterial defense.
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6. GSE319754 RXRα抑制驱动脓毒症中的肝脏代谢和免疫功能障碍：BEX在假手术和CLP（8小时）中诱导基因表达

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune、metabolic
• 📝 描述：Contributors : Matyas Jelinek ; Jolien Vandewalle ; Marah Heyerick ; Tineke Vanderhaeghen ; Céline Van Dender ; Steven Timmermans ; Madeleine Hellemans ; Daria Fijalkowska ; Martin Guilliams ; Karolien De Bosscher ; Claude LibertSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusSepsis is a life-threatening condition where a dysregulated host response to infection causes organ dysfunction and the collapse of metabolic and immune functions. Here, we identify hepatocyte Retinoid X Receptor α (RXRα) as a central integrator of host resilience during polymicrobial sepsis. We show that hepatic Rxra expression is transcriptionally dependent on the upstream regulator Hepatocyte Nuclear Factor 4 α (HNF4α), and that sepsis rapidly suppresses RXRα abundance at both the mRNA and protein levels. Transcriptomic profiling further reveals that the septic liver develops partial resistance to pharmacological RXR activation by its agonist Bexarotene (Bex). Despite this, prophylactic treatment with Bex preserves metabolic stability, enhances bacterial clearance, and improves survival. Using hepatocyte-specific inducible RXRα-deficient mice (RXRαiAlbKO), we demonstrate that this protective effect is strictly dependent on hepatocyte RXRα. Mechanistically, the loss of RXRα in hepatocytes leads to a profound reduction in the liver-resident macrophage, Kupffer cells (KC), resulting in uncontrolled bacterial dissemination and increased mortality. This defect is phenocopied by selective KC depletion. These findings establish that hepatocyte RXRα is essential for maintaining the hepatic macrophage niche, thereby linking hepatocellular transcriptional competence to systemic antibacterial defense.
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7. GSE298027 人类皮层神经元发育过程中保守的NLRC5信号通路是干扰素γ驱动的HLA I类分子表达和神经活动变化所必需的

• ✍️ 作者：未知作者
• 🏷️ 关键词：HLA、pathway
• 📝 描述：Contributors : Michelle K Drews ; Jimena Andersen ; Ji-il Kim ; Melissa Stafford ; Anca M Pasca ; Sergiu P Pasca ; Carla J ShatzSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensMaternal infection and inflammation are linked to increased risk of neurodevelopmental disorders. Here we show that MHC Class I molecules (human: HLA I), which play key roles in brain development, are expressed in neurons in human cortical organoids (hCOs) and human cerebral cortex. These HLA I molecules are significantly upregulated by interferon gamma (IFNg) exposure. Inflammatory mediators downstream of IFNg, including the HLA I enhancer NLRC5, are mechanistically implicated in this upregulation by RNA sequencing IsHhHHLA. NLRC5 KO hCOs fail to undergo developmental increases in neuronal HLA I expression, as well as IFNg-driven HLA I upregulation. Functionally, IFNg exposure lowers spontaneous neural activity in hCOs, which is prevented in NLRC5 KO. These observations link IFNg to human neuronal HLA I expression via NLRC5 and demonstrate a functional consequence on spontaneous activity in a developing neural circuit. Changes in levels and patterns of neural activity associated with elevated HLA I may contribute to the increased risk of altered cortical development and suggest that targeting NLRC5 could mitigate consequences of neuroinflammation.
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8. GSE284445 细胞毒性组织驻留 NK 细胞浸润并控制实体上皮肿瘤生长 [ATAC-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、ATAC-seq
• 📝 描述：Contributors : John B Sunwoo ; Jennifer A Foltz ; Imran MohammadSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensHuman tissue-resident natural killer (trNK) cells – broadly defined by markers of tissue-residency, such as CD49a (integrin alpha1, ITGA1) and CD103 (integrin alpha E, ITGAE) – are increasingly recognized for their immunoregulatory role in host control of infection, malignancy, and autoimmunity. Although the importance of transforming growth factor beta (TGFβ) in trNK cell differentiation has been demonstrated, the context in which the differentiation of CD49a+CD103+ trNK cells occurs can result in either an immunosuppressive phenotype or a highly cytotoxic one. To understand this dichotomy better, we utilized a multiomics approach to molecularly characterize these cells and identified a highly cytotoxic trNK (ctrNK) cell phenotype, characterized by the expression of CD39.
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9. GSE329678 辛伐他汀重编程B16.F10黑色素瘤细胞的代谢，促进早期适应性反应和耐药相关性状

• ✍️ 作者：未知作者
• 🏷️ 关键词：metabolism、resistance
• 📝 描述：Contributors : Giorgiana G Negrea ; Loredana Balacescu ; Ilie O Pavel ; Alina Sesarman ; Manuela BanciuSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusOur previous studies demonstrated that simvastatin (SIM) inhibited B16.F10 murine melanoma cell proliferation in vivo and in vitro via strong suppressing the production of subunit α of hypoxia inducible factor 1 (HIF-1) (HIF-1 α) - a key regulator of cancer cell adaptation to hypoxia. However, beyond its known role in hypoxia, normoxic expression of HIF-1α in melanoma has been linked to increased cancer cell aggressiveness, underscoring its broader impact on tumor biology. Since the translation of HIF-1α is modulated by Akt, SIM effects on both regulatory factors in relation to cancer cell metabolism under normoxia were investigated. SIM effects on cell metabolism were analyzed at mRNA and at protein level. Our data suggested that SIM reprogrammed glucose metabolism to ensure replenishment of tricarboxylic acid (TCA) cycle, favoring its biosynthetic role over its energy role. This shift supported lipid-derived signaling molecules synthesis including isoprenoids and prostaglandins, favoring associated with cell survival and aggressiveness. Our results have important clinical implications, as they emphasize the potential of targeting key lipid metabolic pathways to overcome the adaptive mechanisms driven by normoxic HIF-1α expression. Thus, our data offer promise for novel combination therapies which disrupt the metabolic plasticity of melanoma, to ultimately improve therapeutic outcomes.
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10. GSE312511 STC-15 对 METTL3 的抑制诱导 RNA 错误加工，导致 dsRNA 形成并激活先天免疫 [GLORI]

• ✍️ 作者：未知作者
• 🏷️ 关键词：immunity
• 📝 描述：Contributor : Harry FischlSeries Type : Methylation profiling by high throughput sequencingOrganism : Homo sapiensThe RNA methyltransferase METTL3 is responsible for the generation of m6A, the most abundant modification mark on mRNA and long non-coding RNA. Accumulating evidence suggests numerous roles of METTL3 in cancer initiation and progression and highlights the potential for targeting this enzyme in oncology. STC-15 is a potent and selective METTL3 inhibitor and the first RNA modifying enzyme inhibitor to enter human clinical development. It is structurally related to the previously published tool inhibitors STM2457 and STM3675. We previously identified the induction of a cancer cell-intrinsic interferon response following pharmacological inhibition of METTL3, leading to activation of T-cell-mediated anti-tumour response. Here, we profiled m6A levels at nucleotide resolution using GLORI and characterised RNA changes following METTL3 inhibition with STC-15 or STM3675. Following loss of m6A, we uncovered aberrant mRNA transcripts arising from intron retention (IR) and transcriptional run-on (RO) events downstream of m6A-enriched exons in human cancer cells and in tumour samples in vivo. We found that these IR and RO events produce double-stranded RNA and are bound by the cytoplasmic dsRNA sensor MDA5.Using preclinical in vitro and in vivo models, we characterised in detail the anti-tumour immune responses induced by STC-15. Our study reveals how METTL3 inhibition leads to dsRNA accumulation, which triggers a type I interferon response and induces anti-tumour immunity. Together, these findings provide a mechanistic rationale for STC-15 as a novel anti-cancer drug both as monotherapy and in combination with anti-PD1 checkpoint inhibitors.
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1. 科学家们刚刚发现咖啡对你的肠道和大脑的真正影响

• ✍️ 作者：未知作者
• 🏷️ 关键词：gut、regex:gut(-?microbiome)?
• 📝 描述：Coffee doesn’t just energize—it actively reshapes the gut and mind. Researchers found that both caffeinated and decaf coffee altered gut bacteria in ways linked to better mood and lower stress. Decaf even improved learning and memory, while caffeine boosted focus and reduced anxiety. Together, they show coffee works through multiple pathways beyond just caffeine.
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2. 阿尔茨海默病药物可能无效，甚至可能增加脑部风险。

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer
• 📝 描述：Drugs designed to clear amyloid beta from the brain—once seen as a promising path to slowing Alzheimer’s—may not actually help patients in any meaningful way, according to a major review of over 20,000 participants. Even more concerning, they may increase the risk of brain swelling and bleeding, sometimes without obvious symptoms.
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• GSE329567 新生儿链脲佐菌素诱导糖尿病模型内脏脂肪组织（VAT）转录组分析：姜黄素的调节作用。[RNA-Seq]
• GSE329534 三氯化铁 (FeCl3) 处理下泛菌属、微球菌属、假单胞菌属和赫氏螺菌属的比较转录组分析
• GSE329469 人类诱导多能干细胞来源的心脏祖细胞重现内源性心脏祖细胞功能，为心脏再生提供新的细胞来源
• GSE329416 RNAP-seq：体外全基因组转录揭示艰难梭菌反义DNA上RNA聚合酶的优先暂停
• GSE329212 表观基因组和染色质分析揭示 SPATC1L-COL6A 是儿童肥胖症的一个新的致病基因位点
• GSE313280 小鼠脾脏 CD45+ 红细胞显示出抗原呈递细胞的转录组特征
• GSE297266 TRMT5/NES 协同活动驱动胰腺癌生长和转移 [核糖体测序]
• GSE297265 TRMT5/NES 协同活动驱动胰腺癌生长和转移 [RIP-seq II]
• GSE297264 TRMT5/NES 协同活动驱动胰腺癌生长和转移 [RIP-seq I]
• 利用 NanoString GeoMX DSP 对小鼠胆管癌 (CCA) 的癌症相关成纤维细胞 (CAF)/活化肝星状细胞 (HSC) 进行 GSE296330 转录组分析。
• GSE284447 细胞毒性组织驻留 NK 细胞浸润并控制实体上皮肿瘤生长 [CITE-Seq]
• GSE231733 用 Ad5 空载体 (GFP) 或表达 SARS-CcV-2 核衣壳 (AdN) 的 Ad5 转导的 A549 细胞的批量 RNA 测序
• GSE173882 ELF5 独立于 EHF 调节上皮完整性 [RNA-seq]
• GSE173880 ELF5 独立于 EHF 调节上皮完整性 [ChIP-seq]
• GSE310620 RNA-seq 在缺乏红细胞中 Arg1 表达的小鼠 (RBC.ARG1-KO) 及其同窝对照小鼠 (RBC.ARG1-WT) 的主动脉平滑肌细胞中，于标准 DMEM 或泡沫细胞培养基 (DIAM) 中培养后进行分析。