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1. ⭐ GSE316390 单细胞和空间转录组学揭示心脏移植血管病变中新的免疫-基质相互作用

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune、cardiac、spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributors : Macee C Owen ; Daniel Y Li ; Haewon Shin ; Wenduo Gu ; Alekhya Parvathaneni ; Farid F Kadyrov ; Xiaoran Wang ; Maura Sticco-Ivins ; Hao Dun ; Sariah Hyacinth ; Samantha Giangrasso ; Caroline Chou ; Chieh-Yu Lin ; Michael T Cain ; Albert Pedroza ; Alex Dalal ; Karim Sallam ; Jack Boyd ; Joseph Woo ; Junedh Amrute ; Paul Cheng ; Kory J Lavine ; Benjamin J KopeckySeries Type : OtherOrganism : Homo sapiensCardiac allograft vasculopathy (CAV) is the leading cause of mortality in heart transplant recipients. Despite the prevalence of CAV, there are no targeted therapeutic options to prevent or reverse disease progression, and patients ultimately require retransplant. CAV is characterized by progressive neointimal hyperplasia in donor heart coronary arteries, leading to luminal obliteration and ultimately allograft failure or sudden cardiac death. Although immune and stromal cell interactions are believed to play a key role in CAV pathogenesis, the specific cellular players and molecular signals driving disease remain undefined. In this study, we leverage single-cell RNA sequencing and spatial transcriptomics of human coronary arteries to transcriptionally characterize CAV and define the neointimal microenvironment. We compare arteries with CAV to atherosclerotic coronary artery disease and non-disease controls to identify a unique CAV transcriptional signature. Integration of single-cell RNA sequencing and spatial transcriptomic datasets revealed that modulated vascular smooth muscle cells and macrophage subsets dominate the CAV neointima and suggest that these cells interact to propagate type 1 interferon (IFN)-mediated inflammation. In a mouse CAV model, we demonstrate that interferon blockade with Ruxolitinib significantly reduced the incidence of CAV and prolonged allograft survival. Collectively, this study offers a novel and detailed characterization of the unique cellular and transcriptional landscape of CAV and identify a candidate pathway that may underly CAV pathogenesis, which could serve as a new therapeutic target for this devastating disease.
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2. ⭐ GSE305369 CD40L-CD40通路中CD4+ T细胞辅助受损导致男性肿瘤控制能力下降[MB49肿瘤细胞]

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、T cell、pathway
• 📝 描述：Contributors : Katey S Hunt ; Samantha Cooke ; Lindsey M Kuehm ; Tyson A Lobb ; Emily Ebert ; Smirthi Beeram ; Ryan M Teague ; Michelle Brennan ; Melissa M Berrien-Elliott ; Stephen T Ferris ; Elise AlspachSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusSex-based differences in cancer incidence are incompletely understood, but potential roles for the immune system are beginning to emerge. CD4+ T cells play a central role in organizing antitumor immunity. In addition to cytokine production, CD40L expression on CD4+ T cell provides necessary helper signaling to dendritic cells that is required for the priming of cytotoxic tumor-specific CD8+ T cells. Despite these critical functions, the impact of biological sex on the CD4+ T cell response to cancer remains unknown. Here, we demonstrate that impaired immune-mediated tumor control in male compared to female mice is driven by disparate helper CD4+ T cell responses between the sexes. We find that CD40L expression is reduced on CD4+ T cells isolated from males via a mechanism predominantly driven by sex hormones, resulting in decreased CD40 signaling in dendritic cells within tumor-draining lymph nodes. These deficits resulted in decreased helper CD4+ T cell frequencies and impaired CD8+ T cell function within the male tumor microenvironment which could be rescued by targeting the CD40L-CD40 axis. Our findings identify a novel mechanism of CD4+ T cell-based sex differences in the immune response to cancer that impairs tumor control.
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3. ⭐ GSE305285 CD40L-CD40通路介导的CD4+ T细胞辅助功能受损导致男性肿瘤控制能力下降

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、T cell、pathway
• 📝 描述：Contributors : Katey S Hunt ; Samantha Cooke ; Lindsey M Kuehm ; Tyson A Lobb ; Emily Ebert ; Smirthi Beeram ; Ryan M Teague ; Michelle Brennan ; Melissa M Berrien-Elliott ; Stephen T Ferris ; Elise AlspachSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusSex-based differences in cancer incidence are incompletely understood, but potential roles for the immune system are beginning to emerge. CD4+ T cells play a central role in organizing antitumor immunity. In addition to cytokine production, CD40L expression on CD4+ T cell provides necessary helper signaling to dendritic cells that is required for the priming of cytotoxic tumor-specific CD8+ T cells. Despite these critical functions, the impact of biological sex on the CD4+ T cell response to cancer remains unknown. Here, we demonstrate that impaired immune-mediated tumor control in male compared to female mice is driven by disparate helper CD4+ T cell responses between the sexes. We find that CD40L expression is reduced on CD4+ T cells isolated from males via a mechanism predominantly driven by sex hormones, resulting in decreased CD40 signaling in dendritic cells within tumor-draining lymph nodes. These deficits resulted in decreased helper CD4+ T cell frequencies and impaired CD8+ T cell function within the male tumor microenvironment which could be rescued by targeting the CD40L-CD40 axis. Our findings identify a novel mechanism of CD4+ T cell-based sex differences in the immune response to cancer that impairs tumor control.
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4. ⭐ GSE322659 一氧化氮合酶 2 依赖性代谢紊乱、免疫抑制和转移性三阴性乳腺癌的基因组不稳定性

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、metabolic、regex:immuno(logy|therapy|suppression)
• 📝 描述：Contributor : William R MontfortSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiens ; Mus musculusChronic inflammation drives many diseases, including cancer, where inflammation is associated with metastasis, the cause of death in 90% of cancer fatalities. Tumor inflammation drives inducible nitric oxide synthase (NOS2 or iNOS) and cyclooxygenase 2 (COX2) expression, each of which is associated with poor outcomes in cancer. Here, we knocked out the NOS2 gene in the murine triple negative breast cancer allograft tumor model 4T1 and examined metastatic spread from primary mammary tumors to lung in BALB/c mice with intact immune systems. Remarkably, while the parental 4T1 tumors were highly metastatic, metastasis from 4T1 NOS2-/- tumors was nearly eliminated. In cell culture, we find that nitric oxide from NOS2 induces a glycolytic phenotype, epitrascriptomic dysregulation, DNA damage, and prostaglandin E2 synthesis by stimulating COX2. Human colorectal cancer cell line DLD1 yielded similar results. RNA sequencing revealed NOS2-dependent loss of mRNA associated with regulation of chromosome and DNA replication, including cell cycle checkpoints, as well as mRNA associated with RNA demethylation, including tRNA demethylation. Immunoprofiling of the tumor microenvironment revealed immunosuppressed tumors that were low in T cells and high in myeloid derived suppressor cells expressing interferon gamma, which induces NOS2 expression. Others have shown nitric oxide from immune cells suppresses tumor immunity. Here, we show nitric oxide from tumor cells plays a critical role in metastasis. Taken together, these data suggest high NOS2 in tumor cells drives metastasis through a broad accumulation of cancer-associated factors – including metabolic dysregulation, genetic instability, and immunosuppression – all of which contribute to aggressive metastasis.
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5. ⭐ GSE322570 LIF 诱导的肿瘤可塑性在 LKB1 突变肺癌中建立了免疫抑制性髓系微环境 [RNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、cancer、RNA-seq
• 📝 描述：Contributors : Ray Pillai ; Ali Rashidfarrokhi ; Yuan Hao ; Aristotelis Tsirigos ; Sergei Koralov ; Thales PapagiannakopoulosSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusBulk RNA-seq of sorted Lkb1 wildtype (sgNeo) and Lkb1 mutant (sgLkb1) tumor cells
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6. GSE322794 经皮碳酸氢盐疗法可提高膀胱癌肿瘤内pH值并诱导抗肿瘤反应

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、cancer
• 📝 描述：Contributors : Oluwaseyi Oluwatola ; Sarah Bazargan ; Pietro Irrera ; Darwin Chang ; Ashley Thomas ; Jamie Blauvelt ; Matthew Beatty ; MacLean Hall ; Chrisropher Whelan ; Veronica Estrella ; Katatzyna Rejniak ; Michael Poch ; Nathan Fitzsimmons ; Ryan Beal ; Arig Ibrahim-Hashim ; Shari Pilon-ThomasSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusIntroduction: Tumor acidosis is a hallmark of cancer that leads to abrogation of T cell function and cancer progression. Oral sodium bicarbonate therapy for alkalization of the extracellular tumor pH has shown moderate positive effects in tumor models. However, its applicability in the clinic is very limited due to the unreasonably high dosage required and gastrointestinal disturbances that arise. In this study, we assessed the functional effects of acidity on T cells. Methods: We show that acidity alters T cell proliferation, migration and effector functions as well as transcriptional programming using in vitro culture techniques and RNA sequencing. We then tested the potency of a proprietary transdermal formulation, DYV800, containing sodium bicarbonate to increase the extracellular tumor pH (pHe) and augment anti-tumor immune responses in a murine model of bladder cancer. The tumor pH was assessed using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging (CEST-MRI) and antitumor immune responses via flow cytometry. Results: We found that transdermal DYV800 significantly reduced tumor burden and improved antigen-specific CD8+ T cell responses. Chemical Exchange Saturation Transfer Magnetic Resonance Imaging (CEST-MRI) of treated tumors showed an increase in intra-tumoral pH of bladder tumors, and this therapy also alkalizes the urine. Discussion/Conclusion: The transdermal delivery of DYV800 led to durable anti-tumor immune responses and is more clinically applicable to combat acidity in bladder cancer than oral bicarbonate. Targeting acidosis in the bladder tumor microenvironment has the potential to enhance T cell responses and improve anti-tumor immunity.
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7. GSE319461 DNA甲基化随机性与转录变异性相关，并揭示了AML基因定义亚型中趋同的表观遗传破坏。

• ✍️ 作者：未知作者
• 🏷️ 关键词：epigenetic、methylation
• 📝 描述：Series Type : Expression profiling by high throughput sequencing ; Methylation profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensThis SuperSeries is composed of the SubSeries listed below.
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8. GSE316118 角蛋白 5 表达定义了在高级别浆液性卵巢癌中由层级相关的骨桥蛋白产生微环境维持的癌细胞增殖细胞。

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、carcinoma
• 📝 描述：Contributors : Mallikarjun Bidarimath ; Coulter R Ralston ; Ian M Rose ; Alexander Y NikitinSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensHigh-grade serous carcinoma (HGSC) is the most common and aggressive form of ovarian cancer. Advanced HGSCs display marked cellular heterogeneity. A subset of tumor cells functions as cancer-propagating cells (CPCs, also referred to as cancer stem cells), which are highly tumorigenic and exhibit stem cell-associated properties, including self-renewal and chemoresistance. In contrast, a substantial fraction of HGSC cells is non-tumorigenic. The role of these non-cancer-propagating cells (non-CPCs) and their relationship to CPCs remain poorly understood. Here, we demonstrate that neoplastic cells expressing the intermediate filament protein keratin 5 (KRT5) represent bona fide CPCs. KRT5⁺ cells form cancer organoids over successive passages, are tumorigenic in serial dilution xenograft assays, and are resistant to the antineoplastic agents doxorubicin and cisplatin. Single-cell lineage-tracing experiments show that KRT5⁺ CPCs give rise to KRT5⁻ cells. KRT5⁺ and KRT5⁻ populations exhibit distinct gene expression profiles, with KRT5⁻ cells characterized by expression of SPP1, which encodes the secreted factor osteopontin (OPN). Treatment with OPN enhances HGSC organoid growth and chemoresistance, whereas SPP1 knockdown reverses these effects. Together, these findings support a model in which HGSC contains two hierarchically related cell populations: KRT5⁺, OPN-responsive CPCs and KRT5⁻, non-tumorigenic cells that form a niche producing OPN. Targeting pathways that sustain both stem-like tumor cells and their supportive niche may enable reduced dosing of highly toxic chemotherapeutic agents while enhancing therapeutic efficacy in HGSC.
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9. GSE296658 谷氨酰胺拮抗剂前药重编程树突状细胞以增强结直肠癌免疫疗法

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、regex:immuno(logy|therapy|suppression)
• 📝 描述：Contributors : Gaofei Wei ; Bingjie Zhang ; Renming FanSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe tumor microenvironment (TME) imposes profound metabolic and immunosuppressive barriers that compromise the functionality of immune cells and limit effective anti-tumor responses. A hallmark of many tumors is their heightened dependency on glutamine as a metabolic substrate, which leads to glutamine depletion within the TME. This glutamine scarcity impairs the function of dendritic cells (DCs), resulting in defective antigen presentation and diminished activation of CD8⁺ cytotoxic T cells. Here, we report T26, a bifunctional immunometabolic prodrug composed of JHU083 (a glutamine antagonist) and MSA-2 (a STING agonist), designed to restore DC functionality and enhance anti-tumor immunity. T26 effectively suppresses tumor growth in colorectal cancer (CRC) models by reprogramming the TME toward a more immunostimulatory state. Mechanistically, T26 promotes DC maturation, enhances antigen presentation, and facilitates robust CD8⁺ T cell responses, leading to durable tumor suppression. Importantly, DC depletion experiments demonstrate that the anti-tumor efficacy of T26 is critically dependent on DC activation. Moreover, T26 reprograms tumor-derived extracellular vesicles (EVs), enhancing their capacity to transmit immunostimulatory signals and support CD8⁺ T cell–mediated cytotoxicity. In addition, T26 exhibits strong synergistic effects when combined with standard chemotherapy, immune checkpoint blockade, and anti-angiogenic therapy, further potentiating therapeutic efficacy. Collectively, these findings position T26 as a promising candidate for combination cancer immunotherapy, offering a dual-acting strategy that overcomes metabolic suppression and immune evasion in the TME to improve treatment outcomes.
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10. GSE288434 CAR T 细胞生产过程中 BCL-2 的破坏通过非凋亡适应性改变增强效力 [scRNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：T cell、scRNA
• 📝 描述：Contributors : Nada S Aboelella ; Ryan Park ; Erting Tang ; James L LaBelleSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBH3 mimetics were initially designed to induce cancer cell death through targeting key anti-apoptotic members within the BCL-2 family of proteins. Venetoclax, the only FDA-approved BCL-2-specific BH3 mimetic, has demonstrated robust clinical efficacy in killing acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) cells attributed to its direct apoptotic tumor effect. However, little is known regarding the direct effect of venetoclax on tumor infiltrating T cells. Recent studies have reported apoptosis-independent immunomodulatory activities of venetoclax that still are not fully understood. Given the vital role of BCL-2 family proteins in the dynamic processes of T cell activation, differentiation to effector or memory phenotype and contraction, it becomes imperative to dissect the direct effect of BH3 mimetics on T cell functions. We previously demonstrated that murine T cells expanded for 5 days in vitro in the presence of venetoclax acquire adaptive-like reprograming leading to cell death resistance. Further, long-term in vivo treatment with venetoclax results in transcriptional alterations of signaling pathways involved in T cell activation and exhaustion resistance. Herein, we investigate whether this venetoclax-induced T cell reprograming can be employed to improve the efficacy of adoptive T cell therapy. Using murine and human CD19-targeted chimeric antigen receptor (CAR) T cell therapy (CD19CART) as a model, we show that venetoclax treatment during expansion of CD19CARTs prepared from T cells isolated from healthy donors and patients exhibit enhanced antitumor efficacy in vitro and in vivo using pre-clinical xenograft models of lymphoma and leukemia. Mechanistically, bulk and single-cell RNA sequencing analyses reveal that venetoclax treatment during CART manufacturing transcriptionally reprograms CART cells at key T cell signaling (JAK/STAT5, PI3K/AKT, NFKB) and metabolic (PGC1α, OXPHOS, glycolysis) pathways to enhance CAR T cell fitness and durability, mechanisms dependent upon BCL-2 affinity to venetoclax. Our study highlights a possible novel therapeutic approach to induce adaptive anti-apoptotic reprograming to enhance the efficacy of CAR T cell therapy and supports the continued examination of BH3 mimetics as immune modulators.
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1. ⭐ 空间RNA测序揭示了肠道中微生物和宿主细胞的相互作用方式

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing、spatial、gut、regex:gut(-?microbiome)?
• 📝 描述：A new spatial RNA sequencing approach maps microbial and host gene activity in the gut at micrometer resolution, revealing how microbiome organization and host…
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• GSE323973 乳腺癌高通量测序表达谱分析
• GSE322732 CCAAT增强子结合蛋白δ在急性髓系白血病中发挥抑癌基因的作用
• GSE322668 TKT 和 c-Myc 之间的正反馈回路驱动肝细胞癌的 TACE 耐药性
• GSE322634 LIF 诱导的肿瘤可塑性在 LKB1 突变肺癌中建立了免疫抑制性髓系微环境 [antiLif_CITEseq]
• GSE322633 LIF 诱导的肿瘤可塑性在 LKB1 突变肺癌中建立了免疫抑制性髓系微环境 [sgLif_CITEseq]
• GSE322632 LIF 诱导的肿瘤可塑性在 LKB1 突变肺癌中建立了免疫抑制性髓系微环境 [10x_scRNAseq]
• GSE291548 比目鱼变态发育过程中的表观遗传调控：大菱鲆脑DNA甲基化和基因表达的整合组学分析
• GSE262955 CRIPTO 调控乳腺癌细胞外囊泡摄取和成纤维细胞活化 [批量 RNA 测序]
• GSE316392 淋巴细胞来源的胆碱能回路调节生发中心输出和B细胞活化
• GSE288117 PA200 缺失对肺癌细胞系 A549 和 NCI-H1299 中基因表达的影响
• GSE161222 成年小鼠静脉与主动脉内皮细胞的差异表达模式
• GSE315106 α细胞和β细胞中DNA损伤反应的发育控制塑造了糖尿病中β细胞的选择性易感性[scRNA-Seq]
• GSE315104 α细胞和β细胞中DNA损伤反应的发育控制塑造了糖尿病中β细胞的选择性易感性[RNA-Seq]
• GSE298765 LDOC1 缺失对人 EGFR 突变型 NSCLC PC9 细胞系转录组的影响
• GSE297452 RNA-Seq 分析了经 T26 处理和未处理的 MC38 细胞
• GSE288296 研究表明，CAR-T细胞生产过程中BCL-2的破坏可通过非凋亡性适应性改变增强其效力。
• GSE294453 转移相关伤口修复促进肺上皮和乳腺癌转移灶在转移性生长过程中相互激活
• GSE322669 基于转录组学和网络药理学探索加味兴必补凝胶滴鼻剂治疗儿童过敏性鼻炎的机制
• GSE322617 Khellin 调节 DDIT4 以调控三阴性乳腺癌中的自噬
• GSE322600 CION 或假手术小鼠中投射至 PBN 的 Sp5C 神经元的单神经元测序
• GSE322576 炎症性关节炎免疫相关不良事件代表了一种独特的自身免疫性疾病实体，主要由 T 细胞驱动，但可能并非由自身抗体驱动。
• GSE322537 小鼠干细胞胚胎模型缺乏所有 Hox 功能，存在多种缺陷 [ChIP-Seq]
• GSE307463 碱性五半胱氨酸 1 (BPC1) 参与拟南芥中 camalexin 生物合成的表观遗传抑制
• GSE300433 将 HTT 中间等位基因和 microRNA 失调与晚发性阿尔茨海默病中 tau 蛋白病变的增强联系起来
• GSE262956 CRIPTO 调控乳腺癌细胞外囊泡摄取和成纤维细胞活化 [scRNAseq]
• GSE249068 靶向 Mettl8-Tcf1 轴促进 CD8+ TPEX 分化和抗肿瘤免疫