详细内容（前10条）

1. ⭐ GSE241415 抑制循环甘氨胆酸调节信号通路可通过抑制FBXW7介导的CD73降解，增强免疫检查点疗法在结直肠癌免疫逃逸和抗PD-1免疫疗法耐药中的疗效

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、immune、regex:immuno(logy|therapy|suppression)、resistance
• 📝 描述：Contributors : Senlin Zhao ; Jing Zhang ; Yushuai Mi ; Zijuan Hu ; Xinyang Zhong ; Ye Xu ; Sanjun Cai ; Xinxiang Li ; Ping Wei ; WanJun Chen ; Dawei LiSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusSerum bile acids (BAs) (1) are an important risk factor for the initiation and progression of cancer, but their roles in colorectal cancer (CRC) remain largely unknown. The present study showed that glycocholic acid (GCA), a primary BA, was highly accumulated in the serum of patients with CRC. In a mouse model of CRC, GCA diet promoted programmed death-ligand 1 (PD-L1) expression in tumors, which attenuated CD8+ T cell-mediated antitumor responses in the tumor microenvironment (TME) (2), and promoted the occurrence and development of CRC. Increased PD-L1 expression was caused by the reduction in activity of the BA receptor farnesoid X receptor (FXR). Mechanistically, FXR acted as transcriptional repressor for the transcription factor SRY-box transcription factor 14 (SOX14), and suppressed the palmitoylation and stabilization of PD-L1 by inhibiting the SOX14-mediated expression of zinc finger DHHC-type palmitoyl transferase 9 (DHHC9). Notably, genetically silencing SOX14 and DHHC9 in cancer cells or administering an FXR agonist synergized with anti-PD-1 therapy, leading to reduced tumor growth in GCA-fed mice. Together, the present findings reveal a previously unrecognized mechanism of BA in remodeling the TME to mediate CRC resistance to immunotherapy, which may have clinical implications for developing immunotherapy strategies for patients with CRC.
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2. ⭐ GSE295133 KRASG12C阳性非小细胞肺癌（NSCLC）细胞对KRAS抑制剂索托拉西布的耐药性特征

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、resistance、KRAS
• 📝 描述：Contributors : Hiroaki Kanemura ; Toshiyuki Takehara ; Takeshi Teramura ; Hidetoshi Hayashi ; Kimio YonesakaSeries Type : Expression profiling by arrayOrganism : Homo sapiensInhibitors of KRAS show clinical efficacy for non–small cell lung cancer (NSCLC) positive for the G12C mutation of KRAS, but primary and acquired resistance to these drugs remains a major clinical problem. Activation of EGFR signaling via the MAPK pathway is a key mechanism of such resistance.We used expression data to understand the gene expression profile and identified distinct charactersitics on resistance cells.
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3. ⭐ GSE290264 皮肤 T 细胞淋巴瘤多组学研究揭示进展和治疗耐药性中的单细胞克隆演变 [批量 RNA 测序]

• ✍️ 作者：未知作者
• 🏷️ 关键词：lymphoma、resistance、RNA-seq
• 📝 描述：Contributor : Jacqueline PaytonSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensCutaneous T-cell lymphoma (CTCL) remains a challenging disease due to its significant heterogeneity, therapy resistance, and relentless progression. Multi-omics technologies offer the potential to provide uniquely precise views of disease progression and response to therapy. We present here a comprehensive multi-omics view of CTCL clonal evolution, incorporating exome, whole genome, epigenome, bulk-, single cell (sc) VDJ-, and scRNA- sequencing of 114 clinically annotated serial skin, peripheral blood, and lymph node samples from 35 CTCL patients. We leveraged this extensive dataset to define the molecular underpinnings of CTCL progression in individual patients at single cell resolution with the goal of identifying clinically useful biomarkers and therapeutic targets. Our studies identified a large number of recurrent progression-associated clonal genomic alterations; we highlight mutation of CCR4, PI3K signaling, and PD-1 checkpoint pathways as evasion tactics deployed by malignant T cells. We also identified a gain of function mutation in STAT3 (D661Y) and demonstrated by CUT&RUN-seq that it enhances binding to transcription start sites of genes in Rho GTPase pathways, which we previously reported to have activated chromatin and increased expression in HDACi-resistant CTCL. These data provide further support for a previously unrecognized role for Rho GTPase pathway dysregulation in CTCL progression. A striking number of progression-associated mutations occurred in chromatin methylation modifiers, including EZH2, suggesting that EZH1/2 inhibition may also benefit patients with CTCL. Knowledge of these molecular changes should be leveraged for improved disease monitoring, biomarker-informed clinical trial design, and new therapeutic strategies in this challenging and incurable cancer.
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4. ⭐ GSE321676 同一胃癌患者在对紫杉醇产生耐药性之前（原发性）和之后（耐药性）的两个恶性腹水来源的类器官中硬脑膜的单细胞RNA测序

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、resistance、scRNA
• 📝 描述：Contributors : Leilei Guo ; Wenshuai LiuSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensWe have employed a single sequencing(scRNA-seq) approach using 10× Genomics scRNAseq of organoids to study paclitaxel resistance in gastric cancer(GC). Patient-derived organoids (PDOs) can recapitulate majority aspects of tissue where they are derived from, in terms of specific molecular profiles, divergent phenotypes, concerning growth pattern, response to classical chemotherapy. This study represents the dural scRNA-seq in two organoids derived from malignant ascites of the same GC patient before (Primary) and after (Resistance) resistant to paclitaxel.
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5. ⭐ GSE320429 SIRT6 的表观遗传激活保护衰老的椎间盘 [scRNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：aging、scRNA、epigenetic
• 📝 描述：Contributors : Pranay Ramteke ; Olivia Ottone ; Makarand RisbudSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusAging is one of the important risk factors for Intervertebral disc degeneration, a major contributor to chronic low back and neck pain. Our recent work has demonstrated a promising role for SIRT6, a nuclear NAD⁺- dependent deacetylase and defatty acylase, in maintaining intervertebral disc health with aging. We therefore investigated whether SIRT6 activation improves outcomes of disc health by studying the spinal phenotype of 24-month-old mice treated with a well-studied agonist, MDL-800, for 6 months. Histological studies revealed healthy disc tissue morphology, enhanced cell viability, and lower degeneration scores in mice treated with MDL-800. Further mechanistic insights revealed that SIRT6 activation decreased H3K9ac levels, improved cell phenotype and matrix quality, and reduced the SASP burden in the disc, characterized by decreased abundance of p21, IL-6 and TGF-b. Tissue RNA-Seq, in vitro measurements of histone 3 modifications, and multi-omics ATAC-seq/RNA-seq analyses revealed that SIRT6 activation altered the epigenetic status (decreased H3K9ac, H3K36me3, and H3K79me2) and transcriptomic landscape of disc cells. Notably, MDL-800 treatment increased LC3II levels, indicating enhanced autophagic flux in nucleus pulposus cells. Furthermore, plasma LC-MS and NMR analyses revealed minimal systemic metabolic changes. ScRNA sequencing of splenocytes and bone marrow cells showed a decrease in the proportions of B cells, T cells, and granulocytes, without an altered systemic cytokine profile, indicating good tolerance and the absence of systemic inflammation following MDL-800 treatment. Our study demonstrates that SIRT6 activation modulates autophagy and cell senescence in the disc, underscoring the feasibility of targeting SIRT6 activation as a promising pharmacological strategy to maintain disc health in the aging spine.
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6. GSE322780 PARP1抑制驱动非整倍体癌细胞的ROS抵抗

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、resistance
• 📝 描述：Contributors : Pan Cheng ; Angela Mermerian-Baghdassarian ; Yufeng Wang ; Ze Chen ; Helberth M. Quysbertf ; Pradeep Singh Cheema ; Joseph C. Mays ; Xin Zhao ; Lizabeth Katsnelson ; Sally Mei ; Rohini Shrivastava ; Mirna Bulatovic ; Jiehui Deng ; Markus Schober ; Kwok-Kin Wong ; Teresa DavoliSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAneuploidy—defined as gains and losses of chromosomes—is frequently observed in cancer and has been implicated in promoting tumor progression and metastasis. However, the molecular mechanisms underlying this phenomenon remain poorly understood. By generating new models of aneuploidy, we found that aneuploidy confers remarkable resistance to reactive oxygen species (ROS)-mediated cell death. This resistance is a general consequence of aneuploidy, independent of the specific chromosomes gained or lost. Mechanistically, Poly(ADP-Ribose) Polymerase 1 (PARP1) is suppressed in aneuploid cells, which inhibits PARP1-mediated cell death after ROS (parthanatos). We validated aneuploidy-associated PARP1 suppression across 15 cell models and human tumors, with pronounced effects in metastatic tumors. Importantly, decreased PARP1 levels promote tumor metastasis while increased PARP1 suppresses it. Through a genome-wide CRISPR screen and functional validation, we identified the transcription factor CCAAT/enhancer-binding protein beta (CEBPB) as a critical mediator of PARP1 downregulation and ROS resistance in aneuploid cells. Furthermore, we found that lysosomal dysfunction serves as the upstream mediator of CEBPB activation in aneuploid cells. We propose that aneuploidy-driven CEBPB activation promotes PARP1 suppression, fostering ROS resistance and cancer progression.
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7. GSE315341 利用包括 BET 蛋白和双重 BRG1/BRM 抑制剂在内的组合克服 AML 细胞中 Menin 抑制剂的耐药性 [RNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：resistance、RNA-seq
• 📝 描述：Contributors : Warren Fiskus ; Kapil BhallaSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensMenin inhibitors (MI) disrupt the binding of Menin to MLL1 leading to repression of MLL1 or MLL1-fusion protein (FP) target genes, including reduced levels of HOXA9 and MEIS1 in AML with mtNPM1 or MLL1-r. While MIs are relatively well-tolerated and induce clinical remissions, these are often short-lived due to development of resistance followed by AML relapse. Through repeated shocks with the MI SNDX-50469, a precursor tool compound to revumenib, followed by recovery, we developed MI-resistant (MITR) AML MV4-11 and OCI-AML3 cells. Present studies show that, compared to MI-sensitive parental cells, MITR cells exhibit an altered epigenome, transcriptome and proteome, without Menin mutations. Through a CRISPR screen, novel druggable MI co-enrichments were identified and targeted, including BRD4, SMARCA4, and CREBBP. Co-treatment with the MI and the SMARCA4/SMARCA2 (BRG1/BRM) inhibitor FHD-286 or the BET proteins inhibitor OTX015 (birabresib), synergistically induced in vitro lethality in MITR and MI-resistant AML cells expressing the mutant Menin (M327I), as well as in patient-derived (PD) AML cells with MLL1r or mtNPM1 that exhibited ex vivo resistance to MI. Compared to each drug alone, co-treatment with SNDX-5613 (revumenib) and FHD-286 or OTX015 and FHD-286 significantly reduced the in vivo AML burden and improved survival of the immune depleted mice, without inducing significant toxicity, in the xenograft models of MITR and MI-resistant PD MLLr AML cells. These findings highlight novel, targeted, drug combinations that overcome MI resistance in AML cells with MLL1r or mtNPM1.
• 🔗 查看原文

8. GSE315339 利用 BET 蛋白和双重 BRG1/BRM 抑制剂的组合克服 AML 细胞中 Menin 抑制剂的耐药性 [ChIP-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：resistance、ChIP-seq
• 📝 描述：Contributors : Warren Fiskus ; Kapil BhallaSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensMenin inhibitors (MI) disrupt the binding of Menin to MLL1 leading to repression of MLL1 or MLL1-fusion protein (FP) target genes, including reduced levels of HOXA9 and MEIS1 in AML with mtNPM1 or MLL1-r. While MIs are relatively well-tolerated and induce clinical remissions, these are often short-lived due to development of resistance followed by AML relapse. Through repeated shocks with the MI SNDX-50469, a precursor tool compound to revumenib, followed by recovery, we developed MI-resistant (MITR) AML MV4-11 and OCI-AML3 cells. Present studies show that, compared to MI-sensitive parental cells, MITR cells exhibit an altered epigenome, transcriptome and proteome, without Menin mutations. Through a CRISPR screen, novel druggable MI co-enrichments were identified and targeted, including BRD4, SMARCA4, and CREBBP. Co-treatment with the MI and the SMARCA4/SMARCA2 (BRG1/BRM) inhibitor FHD-286 or the BET proteins inhibitor OTX015 (birabresib), synergistically induced in vitro lethality in MITR and MI-resistant AML cells expressing the mutant Menin (M327I), as well as in patient-derived (PD) AML cells with MLL1r or mtNPM1 that exhibited ex vivo resistance to MI. Compared to each drug alone, co-treatment with SNDX-5613 (revumenib) and FHD-286 or OTX015 and FHD-286 significantly reduced the in vivo AML burden and improved survival of the immune depleted mice, without inducing significant toxicity, in the xenograft models of MITR and MI-resistant PD MLLr AML cells. These findings highlight novel, targeted, drug combinations that overcome MI resistance in AML cells with MLL1r or mtNPM1.
• 🔗 查看原文

9. GSE290557 多组学研究揭示了皮肤T细胞淋巴瘤进展和治疗耐药性中的单细胞克隆演变，揭示了其多组学特征。

• ✍️ 作者：未知作者
• 🏷️ 关键词：lymphoma、resistance
• 📝 描述：Contributor : Jacqueline PaytonSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensCutaneous T-cell lymphoma (CTCL) remains a challenging disease due to its significant heterogeneity, therapy resistance, and relentless progression. Multi-omics technologies offer the potential to provide uniquely precise views of disease progression and response to therapy. We present here a comprehensive multi-omics view of CTCL clonal evolution, incorporating exome, whole genome, epigenome, bulk-, single cell (sc) VDJ-, and scRNA- sequencing of 114 clinically annotated serial skin, peripheral blood, and lymph node samples from 35 CTCL patients. We leveraged this extensive dataset to define the molecular underpinnings of CTCL progression in individual patients at single cell resolution with the goal of identifying clinically useful biomarkers and therapeutic targets. Our studies identified a large number of recurrent progression-associated clonal genomic alterations; we highlight mutation of CCR4, PI3K signaling, and PD-1 checkpoint pathways as evasion tactics deployed by malignant T cells. We also identified a gain of function mutation in STAT3 (D661Y) and demonstrated by CUT&RUN-seq that it enhances binding to transcription start sites of genes in Rho GTPase pathways, which we previously reported to have activated chromatin and increased expression in HDACi-resistant CTCL. These data provide further support for a previously unrecognized role for Rho GTPase pathway dysregulation in CTCL progression. A striking number of progression-associated mutations occurred in chromatin methylation modifiers, including EZH2, suggesting that EZH1/2 inhibition may also benefit patients with CTCL. Knowledge of these molecular changes should be leveraged for improved disease monitoring, biomarker-informed clinical trial design, and new therapeutic strategies in this challenging and incurable cancer.
• 🔗 查看原文

10. GSE322753 M2巨噬细胞来源的外泌体通过抑制ZAKα-p38信号通路来抑制铁死亡，从而改善支气管肺发育不良

• ✍️ 作者：未知作者
• 🏷️ 关键词：macrophage、pathway
• 📝 描述：Contributors : Yahan Pu ; Mingyue Lv ; Ru Yan ; Honglian Zhang ; Lihui Yu ; Weilai Jin ; Le Zhang ; Zhiwei Yu ; Yahui ZhouSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusBackground: Bronchopulmonary dysplasia (BPD) is a common lung disease in premature infants. Hyperoxia-induced oxidative stress and ferroptosis are key pathological mech-anisms leading to alveolar epithelial (AT) cell injury and impaired alveolar development. M2 macrophage-derived exosomes (M2-Exo), as intercellular communication carriers, have potential protective effects in regulating oxidative stress-related diseases, but the molecular mechanism by which they exert effects by regulating ferroptosis in BPD re-mains unclear. Objective: To explore the protective effect of M2-Exo on hyperoxia or inflammation-induced BPD models and clarify its antioxidant mechanism. Method: In vitro AT cell injury models and in vivo BPD models were constructed by hyperoxia or LPS induction. M2-Exo were isolated, identified, and used to intervene in models. Oxidative stress and ferroptosis-related indicators (ROS, MDA, iron accumulation, GPX4), AT cell functional markers (AQP5, SPC), and ZAKα-p38 pathway activation contents were de-tected. ZAKα overexpression was used to verify pathway dependence. Results: M2-Exo intervention significantly enhanced AT cell viability, upregulated the expression of AQP5 and SPC, and reversed alveolar simplification. Concurrently, it effectively sup-pressed hyperoxia or LPS-induced oxidative stress and ferroptosis, as evidenced by re-duced contents of ROS and MDA, diminished iron accumulation, and GPX4 expression. Mechanistically, M2-Exo significantly inhibited the activation of the ZAKα-p38 pathway, and ZAKα overexpression could antagonize the antioxidant, anti-ferroptotic, and AT cell protective effects of M2-Exo. Conclusions: M2-Exo alleviate AT cell oxidative stress and ferroptosis by inhibiting the ZAKα-p38 pathway, thereby improving hyperoxia or in-flammation-induced BPD and providing a new strategy and molecular target for the antioxidant treatment of BPD.
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1. 胰腺癌可能比我们想象的更早开始躲避免疫系统的攻击。

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、immune
• 📝 描述：Using RNA sequencing and spatial transcriptomics, researchers reveal how early pancreatic lesions form structured niches and engage immune-suppressive cells…
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2. 年轻的癌症幸存者面临更快的衰老速度和可能出现的早发性痴呆症

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、aging
• 📝 描述：Surviving cancer at a young age may come with an unexpected cost: faster aging at both the cellular and brain levels. Researchers found that survivors often show signs of being biologically older than their actual age, with chemotherapy accelerating the process most dramatically. This accelerated aging is linked to struggles with memory and focus, which can ripple into education and career outcomes. Encouragingly, scientists believe healthy habits like exercise may help turn back the clock.
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3. 免疫细胞会记住它们的位置。

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune
• 📝 描述：MERLIN uses RNA sequencing data and machine learning to reconstruct where immune cells originated within organs, uncovering region-specific disease mechanisms in kidney and brain tissue…
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4. 科学家发现导致胰腺癌产生化疗耐药性的基因开关

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer
• 📝 描述：Scientists have identified a crucial molecular switch that decides whether pancreatic cancer cells resist chemotherapy or respond to it. The key player, a gene called GATA6, keeps tumours in a more structured and treatable form—but it gets shut down by an overactive KRAS-driven pathway. When researchers blocked that pathway, GATA6 levels rebounded and cancer cells became more sensitive to chemo. The discovery could help turn some of the toughest pancreatic tumours into ones doctors can better control.
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5. 科学家刚刚发现了大脑对抗阿尔茨海默病的隐藏防御机制

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer
• 📝 描述：A new study has uncovered why some brain cells are more resistant to Alzheimer’s damage than others. Researchers found a natural cleanup system that helps remove toxic tau protein before it can form harmful clumps. The study also shows that cellular stress can produce a dangerous tau fragment linked to Alzheimer’s. Strengthening the brain’s natural defenses could point the way to new treatments.
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• GSE322654 RNA-seq 分析衰老细胞中碳骨架介导的代谢重编程：C3N 纳米片和光活化的影响
• GSE320197 SIRT6 的表观遗传激活保护衰老的椎间盘
• GSE291138 利用癌症来源的小细胞外囊泡 (sEV) 的创新型癌症靶向抗体生产策略
• GSE290061 单细胞多组学揭示了 CAR T 细胞在多发性骨髓瘤中持久性和功能的分子驱动因素
• GSE322182 ETV1 激活啮齿动物和人类心肌细胞中的快速传导转录程序 [RNA-Seq]
• GSE319160 脂肪细胞发出信号，从周围细胞募集特定 mRNA 以恢复表达缺陷 [RNA-Seq]
• GSE319159 脂肪细胞发出信号，从周围细胞募集特定的 mRNA 以恢复表达缺陷 [scRNA-Seq]
• GSE311787 研究表明，PAF1C 驱动的 DNA 损伤后 RNAPII 延伸恢复独立于转录相关的组蛋白修饰沉积。
• GSE308889 长读长同工型测序揭示 Aroclor1260 诱导小鼠肝脏中同工型表达
• GSE305522 DHODH 调控前列腺腺癌中的线粒体生物能量学、甲基化循环和 DNA 修复
• GSE291848 脱氧雪腐镰刀菌烯醇和丙烯酰胺对IEC-6肠细胞基因表达的影响
• GSE313867 含有Alu重复序列的RNA在空间上组织核斑周围活跃转录的基因组区域
• GSE296335 小胶质细胞果糖代谢对胶质母细胞瘤生长至关重要
• GSE293114 肝细胞癌研究中二维和三维体外模型的比较分析
• GSE162886：用IL-4刺激24小时后，野生型和MafB敲除巨噬细胞的转录组分析
• GSE322767 肌成纤维细胞编程阻断胰腺癌中TLS组织成纤维网状细胞的分化
• GSE319906 屋尘螨提取物通过两种不同的机制增强果蝇对微生物感染的宿主防御能力
• GSE291102 解析 Myf6 在促进成纤维细胞转化为肌源性祖细胞和分化细胞中的作用 [scRNA-Seq]
• GSE291101 解析 Myf6 在促进成纤维细胞转化为肌源性祖细胞和分化细胞中的作用 [RNA-Seq]
• GSE291099 解析 Myf6 在促进成纤维细胞转化为肌源性祖细胞和分化细胞中的作用 [ATAC-Seq]
• GSE291074 单管 RNA-Seq 揭示 β-catenin 上磷酸化 T551/S552 调控的信号通路
• GSE279379 单核细胞通过涉及 CD44 和 Moesin 的细胞间相互作用诱导乳腺癌细胞表达 PD-L1。
• GSE261365 温度依赖性性别决定中雄性特异性通路转录调控