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1. ⭐ GSE319479 血管表型中的表观遗传转换增强抗肿瘤免疫力 [scRNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、immunity、scRNA、epigenetic
• 📝 描述：Contributors : Dae Joong Kim ; Mitchell McGinty ; Swetha Anandh ; Caroline Riedstra ; Yuvraj Sethi ; Melanie Rutkowski ; Andrew DudleySeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe abnormal tumor vasculature can present a barrier to the infiltration of anti-tumor immune cells, which impairs immune surveillance and response to immunotherapy. Here, we show that targeting the epigenetic factor DNA methyltransferase 1 in endothelial cells (ECs) results in reduced angiogenesis while imparting profound changes to the tumor immune microenvironment (TIME), including increased proportions of CD4+ memory T-cells and NK cells. Depleting CD4+ T-cells, or blocking lymphocyte egress from the lymph nodes with FTY720, rescues tumor growth in mice with conditional deletion of Dnmt1 in ECs (Dnmt1iECKO) and dramatically shortens overall survival, whereas NK cells are dispensable. Tumors implanted in Dnmt1iECKO mice show reduced vascular branching, elevated expression of Vcam1, increased vessel-associated T-cells, and a shift in vascular specification including increased proportions of immune-permissive post-capillary venules (PCVs) and interferon-stimulated ECs (IFN_x0002_ECs). Deleting Dnmt1 in EC cultures strikingly potentiates responses to combinations of IFNg and TNFa and, notably, up-regulates important T-cell co-stimulatory molecules for memory CD4+ T-cells, including Icosl, Cd40, and Tnfsf4. Finally, immune checkpoint blockade (ICB) administered to Dnmt1iECKO mice with experimental melanoma lung metastasis reduces tumor burden, with some mice showing tumor eradication. Our findings identify endothelial Dnmt1 as a key regulator of vascular-mediated anti-tumor immunity, providing a rationale for integrating epigenetic modulation of the vasculature with cancer immunotherapy regimens.
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2. ⭐ GSE318850 淋巴结-肿瘤耗竭T细胞克隆演化的时空图谱

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、lymph、T cell、regex:lymph(o|atic)?
• 📝 描述：Contributors : Yang Zhang ; Haiquan ChenSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensCurrent surgical guidelines overlook preserving uninvolved lymph nodes (uiLNs) in non-small cell lung cancer, principally stemming from an underappreciation of their critical role in anti-tumor immunity. Here, we discovered a significant immunosuppressive microenvironment in metastatic lymph nodes. In contrast, CD200+ progenitor exhausted T cells (Tpex) markedly expanded within uiLNs following immunotherapy. Effective clonal sharing of exhausted T cells between uiLNs and tumors correlated strongly with complete pathological response. Previously unrecognized tumor-resident C1QA+ dendritic cells secreted CXCL9, facilitating T cell recruitment, whereas fibroblast-enriched neighborhoods in non-responders created immunosuppressive barriers hindering CXCL9 diffusion and CD200+ Tpex migration. Finally, we confirmed that tumor-reactive Tex clones from uiLNs could persist systemically and identified two neoantigen peptides as direct targets of these tumor-reactive Tex cells. Our study unprecedentedly elucidates the spatiotemporal dynamics of immunotherapy-responsive T cell subsets in LN-tumor axis and provides compelling evidence to support selective LN dissection strategies to preserve uiLNs.
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3. ⭐ GSE319480 血管表型中的表观遗传转换增强抗肿瘤免疫力 [bulkRNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、immunity、epigenetic
• 📝 描述：Contributors : Dae Joong Kim ; Mitchell McGinty ; Swetha Anandh ; Caroline Riedstra ; Yuvraj Sethi ; Melanie Rutkowski ; Andrew DudleySeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe abnormal tumor vasculature can present a barrier to the infiltration of anti-tumor immune cells, which impairs immune surveillance and response to immunotherapy. Here, we show that targeting the epigenetic factor DNA methyltransferase 1 in endothelial cells (ECs) results in reduced angiogenesis while imparting profound changes to the tumor immune microenvironment (TIME), including increased proportions of CD4+ memory T-cells and NK cells. Depleting CD4+ T-cells, or blocking lymphocyte egress from the lymph nodes with FTY720, rescues tumor growth in mice with conditional deletion of Dnmt1 in ECs (Dnmt1iECKO) and dramatically shortens overall survival, whereas NK cells are dispensable. Tumors implanted in Dnmt1iECKO mice show reduced vascular branching, elevated expression of Vcam1, increased vessel-associated T-cells, and a shift in vascular specification including increased proportions of immune-permissive post-capillary venules (PCVs) and interferon-stimulated ECs (IFN_x0002_ECs). Deleting Dnmt1 in EC cultures strikingly potentiates responses to combinations of IFNg and TNFa and, notably, up-regulates important T-cell co-stimulatory molecules for memory CD4+ T-cells, including Icosl, Cd40, and Tnfsf4. Finally, immune checkpoint blockade (ICB) administered to Dnmt1iECKO mice with experimental melanoma lung metastasis reduces tumor burden, with some mice showing tumor eradication. Our findings identify endothelial Dnmt1 as a key regulator of vascular-mediated anti-tumor immunity, providing a rationale for integrating epigenetic modulation of the vasculature with cancer immunotherapy regimens.
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4. ⭐ GSE307937 PKM2 乳酸化促进结直肠癌血管生成拟态和对贝伐单抗治疗的耐药性，通过促进 FOSL1 超级增强子形成 [RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、resistance、RNA-seq
• 📝 描述：Contributors : Weihao Li ; Jianhong Peng ; Jiahua He ; Zhizhong Pan ; Chi Zhou ; Junzhong LinSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensDespite the clinical utility of bevacizumab in advanced colorectal cancer (CRC), resistance remains a major challenge. Here, we unveiled a lactate-mediated mechanism driving vasculogenic mimicry (VM) and bevacizumab resistance through PKM2 lactylation. PKM2 lactylation at K206 by AARS1 promoted PKM2 nuclear translocation and interaction with FOSL1. PKM2 binding facilitated FOSL1-dependent super-enhancer formation and target gene transcription, which contributed to CRC cell VM. Genetic or pharmacological inhibition of PKM2 lactylation disrupted VM and synergized with bevacizumab in patient-derived pre-clinical models, significantly improving therapeutic efficacy. Together, this study reveals lactylation as a metabolic switch linking cancer glycolytic reprogramming to transcriptional rewiring and proposes targeting PKM2 lactylation to enhance the anti-tumor activity of bevacizumab in CRC.
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5. ⭐ GSE307935 PKM2 乳酸化促进结直肠癌血管生成拟态和对贝伐单抗治疗的耐药性，其机制是通过促进 FOSL1 超级增强子的形成 [ATAC-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、resistance、ATAC-seq
• 📝 描述：Contributors : Weihao Li ; Jianhong Peng ; Jiahua He ; Zhizhong Pan ; Chi Zhou ; Junzhong LinSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensDespite the clinical utility of bevacizumab in advanced colorectal cancer (CRC), resistance remains a major challenge. Here, we unveiled a lactate-mediated mechanism driving vasculogenic mimicry (VM) and bevacizumab resistance through PKM2 lactylation. PKM2 lactylation at K206 by AARS1 promoted PKM2 nuclear translocation and interaction with FOSL1. PKM2 binding facilitated FOSL1-dependent super-enhancer formation and target gene transcription, which contributed to CRC cell VM. Genetic or pharmacological inhibition of PKM2 lactylation disrupted VM and synergized with bevacizumab in patient-derived pre-clinical models, significantly improving therapeutic efficacy. Together, this study reveals lactylation as a metabolic switch linking cancer glycolytic reprogramming to transcriptional rewiring and proposes targeting PKM2 lactylation to enhance the anti-tumor activity of bevacizumab in CRC.
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6. GSE304885 肠道浆细胞样树突状细胞优先产生干扰素λ [scRNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：scRNA、regex:intestin(e|al)
• 📝 描述：Contributors : David A Constant ; Timothy J NiceSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Mus musculusThe healthy intestine mounts immune responses to microbiota to maintain homeostasis, which includes basal production of interferon cytokines. Previous work showed that Type III Interferon (IFN-λ) stimulates localized pockets of interferon-stimulated genes (ISGs) in the adult mouse intestinal epithelium at homeostasis that provide preemptive protection from viral pathogens. Here, we demonstrate that a major source of homeostatic IFN-λ production in the intestine is a population of epithelium-associated plasmacytoid dendritic cells (pDC). These pDC are recruited to the intestine by bacterial microbiota colonization, and pDC depletion or bone marrow reconstitution with IFN-λ-deficient pDC results in reduced homeostatic ISGs in the intestinal epithelium. Notably, intestinal pDC preferentially produce IFN-λ over Type I IFNs whereas splenic pDC produce more Type I IFNs. Comparison of splenic and intestinal pDC reveal tissue-specific changes in gene expression and genomic accessibility, including evidence of response to transforming growth factor beta (TGF-β) in the intestine. Isolated gut pDC produce more IFN-λ that splenic pDC upon stimulation, and pre-treatment of a human pDC cell line with TGF-β results in enhanced production of IFN-λ upon stimulation. This study implicates pDC as important sources of homeostatic IFN-λ in the intestine and defines the role of barrier cytokine TGF-β in regulating IFN types produced by pDC upon stimulation. Reprogramming of recruited pDC by tissue cytokines may have important implications for balancing effective antimicrobial responses with damaging inflammation at barrier tissues.
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7. GSE304884 肠道浆细胞样树突状细胞优先产生干扰素λ [ATAC-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：ATAC-seq、regex:intestin(e|al)
• 📝 描述：Contributors : David A Constant ; Timothy J NiceSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusThe healthy intestine mounts immune responses to microbiota to maintain homeostasis, which includes basal production of interferon cytokines. Previous work showed that Type III Interferon (IFN-λ) stimulates localized pockets of interferon-stimulated genes (ISGs) in the adult mouse intestinal epithelium at homeostasis that provide preemptive protection from viral pathogens. Here, we demonstrate that a major source of homeostatic IFN-λ production in the intestine is a population of epithelium-associated plasmacytoid dendritic cells (pDC). These pDC are recruited to the intestine by bacterial microbiota colonization, and pDC depletion or bone marrow reconstitution with IFN-λ-deficient pDC results in reduced homeostatic ISGs in the intestinal epithelium. Notably, intestinal pDC preferentially produce IFN-λ over Type I IFNs whereas splenic pDC produce more Type I IFNs. Comparison of splenic and intestinal pDC reveal tissue-specific changes in gene expression and genomic accessibility, including evidence of response to transforming growth factor beta (TGF-β) in the intestine. Isolated gut pDC produce more IFN-λ that splenic pDC upon stimulation, and pre-treatment of a human pDC cell line with TGF-β results in enhanced production of IFN-λ upon stimulation. This study implicates pDC as important sources of homeostatic IFN-λ in the intestine and defines the role of barrier cytokine TGF-β in regulating IFN types produced by pDC upon stimulation. Reprogramming of recruited pDC by tissue cytokines may have important implications for balancing effective antimicrobial responses with damaging inflammation at barrier tissues.
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8. GSE297859 半胱天冬酶 3 和 7 通过调节干细胞功能和 gsdmd 介导的细胞焦亡来限制肠道炎症

• ✍️ 作者：未知作者
• 🏷️ 关键词：inflammation、regex:intestin(e|al)
• 📝 描述：Contributors : Xie Wei ; Verstraeten Bruno ; Vandenabeele PeterSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusAberrant intestinal epithelial cell (IEC) death is a hallmark of inflammatory bowel disease (IBD), observed in patient samples and animal models of colitis. While multiple cell death pathways contribute to disease pathogenesis, the dominant modalities and their regulatory mechanisms in IBD remain poorly defined. In this study, we demonstrate that mice with intestinal epithelial cell-specific deletion of caspase-3 and -7 (Casp3/7 Tg) exhibit exacerbated colitis, increased mortality, and impaired epithelial regeneration, phenotypes not observed in other cell death-related knockout models. These findings highlight a previously unrecognized protective role of caspase-3/7 in controlling inflammation and tissue regeneration following intestinal injury. Mechanistically, caspase-3/7 deficiency negatively affects intestinal stem cell proliferation and promotes GSDMD-dependent pyroptosis, compromising barrier integrity and return to steady state conditions. Together, our results identify caspase-3/7 as key regulators of epithelial integrity and inflammation and suggest their modulation as a promising therapeutic strategy in IBD and colorectal cancer.
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9. GSE240483 NAD+ 控制心脏衰老过程中的昼夜节律

• ✍️ 作者：未知作者
• 🏷️ 关键词：aging、cardiac
• 📝 描述：Contributors : Bryce J Carpenter ; Margaux Lecacheur ; Yannick N Mangold ; Kai Cui ; Stefan Günther ; Marit W Vermunt ; Pieterjan DierickxSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusDisruption of the circadian clock as well as reduced NAD+ levels are both hallmarks of aging. While circadian rhythms and NAD+ metabolism have been linked in heart disease, their relationship during cardiac aging is less clear. Here, we show that aging leads to disruption of diurnal gene expression in the heart. Long-term supplementation with the NAD+ precursor nicotinamide riboside (NR) boosts NAD+ levels, reprograms the diurnal transcriptome, and reverses naturally occurring cardiac enlargement in aged female mice. In addition, drastic reduction of NAD+ levels in CMs impairs PER2::luc oscillations, which is rescued by NR supplementation. Finally, we demonstrate that changes to the cardiac transcriptome due to NR treatment partially depend on the activity of SIRT1. These findings reveal an essential role for NAD+ in regulation of the cardiac circadian clock upon aging, which opens up new avenues to counteract age-related cardiac disorders.
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10. GSE309277 一种简单的液态3D细胞培养模型模拟了与肺转移相关的上皮乳腺癌细胞的氧化线粒体代谢

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、metabolism
• 📝 描述：Contributors : Balamurugan Kuppusamy ; Esta SterneckSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensThree-dimensional (3D) cell culture systems have emerged as powerful tools to model tumor biology ex vivo. However, the diverse array of 3D culture methods available presents challenges in selecting the most appropriate model for specific research questions. This study provides a comparative analysis of breast cancer cells (SUM149, IBC-3, MDA-MB-468) in the mammosphere culture (SphC) model or an “emboli” culture (EmC) model, which enrich for cancer stem cells and epithelial features, respectively. The EmC model, designed originally for inflammatory breast cancer, is characterized by media viscosity and mechanical rocking of the culture vessel. Notably, cells in EmC showed a distinct and durable reduction in cell proliferation while demonstrating increased capacity to establish experimental lung metastases. Quantitative analysis of electron microscopy images suggested that cells in EmC acquire nuclear and mitochondrial features that resemble those of tumor tissue. Proteomics, single-cell transcriptomics, and metabolic flux analyses showed that cells in EmC and SphC favor mitochondrial oxidative metabolism (OXPHOS) and glycolysis, respectively. EmC rendered cells hypersensitive to OXPHOS inhibition, yet more resistant to oxidative stress. Several genes associated with lung metastasis, including ID1, were specifically enriched in EmC. Given the increasingly recognized role of OXPHOS in cancer cell survival during dissemination and as established metastases, we propose that the EmC paradigm is a suitable ex vivo model to study signaling pathways relevant for tumor tissue and to assess drug sensitivities and resistance mechanisms of metastatic breast cancer cells ex vivo
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1. 完整氨酰化tRNA的纳米孔测序

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing
• 📝 描述：Using RNA sequencing with nanopore technology, researchers developed aa tRNA seq to identify amino acids attached to individual tRNAs, revealing how modifications influence tRNA stability and charging fidelity…
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• GSE305432 FOXA1/FOXM1 ChIP-seq 在 giredestrant 耐药的 ER+ 乳腺癌细胞系中的应用
• GSE303505 上皮-间质转化与三阴性乳腺癌的免疫组成和细胞毒性功能改变相关
• GSE295127 对耐吉瑞地司他汀的 ER+ 乳腺癌细胞系进行 RNA 测序
• GSE304155 HE4 通过 IFN-γR-STAT3 轴上调巨噬细胞上的 PD-L1 表达来调节抗癌免疫逃逸 [LLC 肿瘤，scRNA-seq]
• GSE298587 HE4 通过 IFN-γR-STAT3 轴上调巨噬细胞上的 PD-L1 表达来调节抗癌免疫逃逸 [RNA-Seq - 细胞系]
• GSE319496 转移性肾细胞癌患者接受纳武利尤单抗联合伊匹木单抗治疗期间，血液参数、全血转录组谱与免疫相关不良事件之间的关联
• GSE319387 乳腺癌血清 tsRNA-Gly-5-0006：差异表达及其对癌细胞生物学的影响
• GSE319070 SMARCA4 通过 H3K27 乙酰化调控 PROX1 促进前列腺癌细胞的谱系可塑性和恩扎卢胺耐药性
• GSE307936 PKM2 乳酸化促进结直肠癌血管生成拟态和对贝伐单抗治疗的耐药性，通过促进 FOSL1 超级增强子的形成 [CUT&Tag]
• GSE230908 对免疫组织和器官的单细胞分析揭示了雄性恒河猴的免疫衰老特征
• GSE306946 缺失 Norrin/β-catenin 信号通路组分或 KIF11 或 PRDX1 的 HREC 的 RNA-SEQ
• GSE305756 小鼠视网膜血管细胞单细胞转录组分析揭示了家族性渗出性玻璃体视网膜病变的机制。
• GSE304886 肠道浆细胞样树突状细胞优先产生干扰素λ
• GSE296138 免疫检查点抑制剂对人源化嵌合小鼠模型肾脏的影响。
• GSE312696 雌激素受体α通过调节VAT Tregs (oVAT)来抵抗肥胖引起的代谢功能障碍
• GSE304776 LGR5⁺干细胞在肠上皮细胞的再生层级中保持顶端位置，无论是在稳态还是损伤状态下
• GSE303999 scRNA-seq揭示滑膜组织中端粒细胞的转录谱
• GSE295128 ATACseq 对 giredestrant 耐药的 ER+ 乳腺癌细胞系
• GSE294200 雌激素受体α通过调节内脏脂肪组织调节因子（VAT Tregs）来抵抗肥胖引起的代谢功能障碍
• GSE291529 利用全基因组 CRISPR 筛选鉴定调控 PFOS 细胞毒性反应的功能性遗传成分
• GSE267725 核受体 ESRRA 通过对超级增强子和启动子的双重作用来调节基因转录程序，从而促进 ERα 阳性乳腺癌的发生发展
• GSE267724 核受体 ESRRA 通过对超级增强子和启动子的双重作用来调节基因转录程序，从而促进 ERα 阳性乳腺癌的发生。
• GSE313133 HE4 通过 IFN-γR-STAT3 轴上调巨噬细胞上的 PD-L1 表达来调节抗癌免疫逃逸 [L1MKK]
• GSE308759 C57BL/6小鼠缺血/再灌注损伤后的转录组变化
• GSE298300 HE4 通过 IFN-γR-STAT3 轴上调巨噬细胞上 PD-L1 的表达，从而调控抗肿瘤免疫逃逸。
• GSE296417 CTCF 在红系分化过程中调节 HBAD 基因启动子的染色质可及性 [ChIP-Seq]
• GSE317352 早期辅助抗PD-L1疗法可改善小鼠肺毛霉菌病的预后并逆转免疫麻痹
• GSE312091 RNA-seq 分析了经 Nr4a1 激动剂细胞孢子酮 B 处理的 SKG 小鼠中 TCR 刺激的 CD4⁺ T 细胞。
• GSE290820 工程改造固有无序区 (IDR) 以引导基因组导航
• GSE289561 Long-term chronic exposure of mice to sodium fluoride and a mixture of endocrine disruptors lead to easily observable tooth enamel and retina abnormalities underlying changes in hepatic metabolism
• GSE286416 多尺度酪氨酸激酶抑制剂心脏毒性分析揭示机械敏感性离子通道 PIEZO1 具有心脏保护作用
• GSE126178 铬暴露的时间进程（RNA-Seq）