详细内容（前10条）

1. ⭐ GSE319598 谱系身份决定了 KRAS 抑制剂耐药小鼠 NSCLC 模型中的癌基因依赖性 [scRNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：regex:onco(logy|logist|gene|genic)、resistance、scRNA、KRAS
• 📝 描述：Contributors : Nicolas Mathey-Andrews ; Carrie L Rodriguez ; Bing Shui ; Agata L Patriotis ; William M Rideout III ; Victor Z Chen ; Ileana Murazzi ; Milton R Cornwall-Brady ; Manyuan Liu ; Morgan Heileman ; Marianna Trakala ; Carla P Concepcion ; Dian Yang ; Tyler JacksSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusPrimary and acquired resistance to targeted therapy represent significant challenges to durable treatment responses in cancer. In lung cancer and other cancer types, allele- specific and pan-KRAS inhibitors offer new promise, but these are hampered by incomplete responses as well as genetic and non-genetic mechanisms of acquired resistance. To model these mechanisms, we treat genetically engineered mouse models of KrasG12C-driven lung cancer with sotorasib, a KRASG12C inhibitor, until the emergence of drug resistance. The initial response to sotorasib was rapid, but incomplete. Residual tumor burden transcriptionally resembled the alveolar type II cell, phenocopying residual disease signatures identified in patients treated with EGFR inhibitors. After continued sotorasib treatment, we observed diverse mechanisms of drug resistance in vivo, including genetic MAPK reactivation and lineage transformation from adenocarcinoma to squamous histology. Focusing mechanistic studies on squamous transformation, we showed that expression of the basal transcription factor ∆Np63 is sufficient to rewire transformed alveolar organoids to a squamous state in vitro, conferring insensitivity to KRAS inhibition. In vivo, either ectopic expression of Sox2 or loss of Nkx2-1, which are tolerated during Kras-driven tumorigenesis, poised tumors for squamous lineage commitment upon KRAS inhibition. Squamous- transformed tumors did not exhibit evidence of KRAS/MAPK reactivation, underscoring the role for lineage transcription factors and histologic transformation in mediating oncogene independence.
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2. ⭐ GSE319597 谱系身份决定了 KRAS 抑制剂耐药小鼠 NSCLC 模型中的癌基因依赖性 [RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：regex:onco(logy|logist|gene|genic)、resistance、RNA-seq、KRAS
• 📝 描述：Contributors : Nicolas Mathey-Andrews ; Carrie L Rodriguez ; Bing Shui ; Agata L Patriotis ; William M Rideout III ; Victor Z Chen ; Ileana Murazzi ; Milton R Cornwall-Brady ; Manyuan Liu ; Morgan Heileman ; Marianna Trakala ; Carla P Concepcion ; Dian Yang ; Tyler JacksSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusPrimary and acquired resistance to targeted therapy represent significant challenges to durable treatment responses in cancer. In lung cancer and other cancer types, allele- specific and pan-KRAS inhibitors offer new promise, but these are hampered by incomplete responses as well as genetic and non-genetic mechanisms of acquired resistance. To model these mechanisms, we treat genetically engineered mouse models of KrasG12C-driven lung cancer with sotorasib, a KRASG12C inhibitor, until the emergence of drug resistance. The initial response to sotorasib was rapid, but incomplete. Residual tumor burden transcriptionally resembled the alveolar type II cell, phenocopying residual disease signatures identified in patients treated with EGFR inhibitors. After continued sotorasib treatment, we observed diverse mechanisms of drug resistance in vivo, including genetic MAPK reactivation and lineage transformation from adenocarcinoma to squamous histology. Focusing mechanistic studies on squamous transformation, we showed that expression of the basal transcription factor ∆Np63 is sufficient to rewire transformed alveolar organoids to a squamous state in vitro, conferring insensitivity to KRAS inhibition. In vivo, either ectopic expression of Sox2 or loss of Nkx2-1, which are tolerated during Kras-driven tumorigenesis, poised tumors for squamous lineage commitment upon KRAS inhibition. Squamous- transformed tumors did not exhibit evidence of KRAS/MAPK reactivation, underscoring the role for lineage transcription factors and histologic transformation in mediating oncogene independence.
• 🔗 查看原文

3. ⭐ GSE319596 谱系身份决定了 KRAS 抑制剂耐药小鼠 NSCLC 模型中的癌基因依赖性 [ATAC-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：regex:onco(logy|logist|gene|genic)、resistance、ATAC-seq、KRAS
• 📝 描述：Contributors : Nicolas Mathey-Andrews ; Carrie L Rodriguez ; Bing Shui ; Agata L Patriotis ; William M Rideout III ; Victor Z Chen ; Ileana Murazzi ; Milton R Cornwall-Brady ; Manyuan Liu ; Morgan Heileman ; Marianna Trakala ; Carla P Concepcion ; Dian Yang ; Tyler JacksSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusPrimary and acquired resistance to targeted therapy represent significant challenges to durable treatment responses in cancer. In lung cancer and other cancer types, allele- specific and pan-KRAS inhibitors offer new promise, but these are hampered by incomplete responses as well as genetic and non-genetic mechanisms of acquired resistance. To model these mechanisms, we treat genetically engineered mouse models of KrasG12C-driven lung cancer with sotorasib, a KRASG12C inhibitor, until the emergence of drug resistance. The initial response to sotorasib was rapid, but incomplete. Residual tumor burden transcriptionally resembled the alveolar type II cell, phenocopying residual disease signatures identified in patients treated with EGFR inhibitors. After continued sotorasib treatment, we observed diverse mechanisms of drug resistance in vivo, including genetic MAPK reactivation and lineage transformation from adenocarcinoma to squamous histology. Focusing mechanistic studies on squamous transformation, we showed that expression of the basal transcription factor ∆Np63 is sufficient to rewire transformed alveolar organoids to a squamous state in vitro, conferring insensitivity to KRAS inhibition. In vivo, either ectopic expression of Sox2 or loss of Nkx2-1, which are tolerated during Kras-driven tumorigenesis, poised tumors for squamous lineage commitment upon KRAS inhibition. Squamous- transformed tumors did not exhibit evidence of KRAS/MAPK reactivation, underscoring the role for lineage transcription factors and histologic transformation in mediating oncogene independence.
• 🔗 查看原文

4. ⭐ GSE224375 维生素 C 通过 DNA 去甲基化对 T 细胞进行表观遗传调控 [RNAseq T 细胞亚型]

• ✍️ 作者：未知作者
• 🏷️ 关键词：T cell、RNAseq、epigenetic
• 📝 描述：Contributors : Xiaolei Hao ; Lu Bai ; Beisi Xu ; Yongqiang FengSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusMaintenance of T cell naïve (Tn) state and restricting effector T cell differentiation upon basal level stimulations would be critical for immune homeostasis and prevention of autoimmunity. To understand how Tn state is regulated by nutrient cues in a cell-intrinsic manner, here we perform an in vivo CRISPR screening to identify required solute carrier (SLC) proteins that transport metabolites and ions into T cells. Among SLC proteins revealed by this experiment, vitamin C transporter Slc23a2 appears to play a role. Conditional ablation of Slc23a2 in T cells by genetic approaches reduces intracellular vitamin C levels by approximately 80%, accompanied by spontaneous activation and differentiation of Tn cells, autoantibody production, and autoimmune pathology in select organs. Slc23a2-deficient Tn cells exhibit profound DNA hypermethylation, dysregulation of genes controlling signaling transduction and transcription, and enhanced differentiation of helper T cells upon stimulation. These results define a broad regulatory space of vitamin C as a cofactor of Tet enzymes in controlling active DNA demethylation. In agreement, conditional deletion of Tet genes impairs Tn state and increases helper T cell differentiation. Thus, our study reveals a cell-intrinsic mechanism by which micronutrient vitamin C via Slc23a2 maintains Tn state and self-tolerance by promoting Tet-mediated DNA demethylation.
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5. ⭐ GSE319747 谱系身份决定了小鼠非小细胞肺癌KRAS抑制剂耐药模型中癌基因的依赖性。

• ✍️ 作者：未知作者
• 🏷️ 关键词：regex:onco(logy|logist|gene|genic)、resistance、KRAS
• 📝 描述：Series Type : Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencingOrganism : Mus musculusThis SuperSeries is composed of the SubSeries listed below.
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6. GSE328221 急性雷帕霉素治疗揭示了母体炎症小鼠模型中功能障碍的新机制 [scRNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：inflammation、scRNA
• 📝 描述：Contributors : Janel LeBelle ; Harley Kornblum ; Kaleab Tessema ; Riki Kawaguchi ; Lindsey DudleySeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensMaternal inflammatory response (MIR) during early gestation in mice induces a cascade of physiological and behavioral changes that have been associated with autism spectrum disorder (ASD). In a prior study and the current one, we find that mild MIR results in chronic systemic and brain inflammation, mTOR pathway activation, mild brain overgrowth followed by regionally specific volumetric changes, sensory processing dysregulation, and social and repetitive behavior abnormalities. Prior studies of rapamycin treatment in autism models have focused on chronic treatments that alter or prevent physical brain changes. Here, we have focused on the acute effects of rapamycin to uncover novel mechanisms of dysfunction related to mTOR pathway signaling. We find that within 2 hours, rapamycin treatment could rapidly rescue neuronal hyper-excitability, seizure susceptibility, functional network connectivity and brain community structure, repetitive behaviors, and sensory over-responsivity in adult offspring with persistent mild brain overgrowth. These CNS-mediated effects are also associated with alteration of the expression of several ASD-, ion channel-, and epilepsy-associated genes in the same time frame. Reduction of microglia with CSF1R inhibitors or inhibition of NADPH oxidase in young animals reduces the development of some of the behavioral phenotypes, but neither is as effective as acute mTOR inhibition. Our findings indicate that mTOR dysregulation in MIR offspring is a key contributor to various levels of brain dysfunction. However, we demonstrate that the adult MIR brain is also amenable to rapid normalization of these functional changes which results in the rescue of both core and comorbid ASD-like behaviors in adult animals without requiring long-term physical alterations to the brain. Restoring excitatory/inhibitory imbalance and sensory functional network modularity may therefore be important targets for therapeutically addressing both primary sensory and compensatory repetitive behavior phenotypes.
• 🔗 查看原文

7. GSE328220 急性雷帕霉素治疗揭示了母体炎症小鼠模型中功能障碍的新机制 [RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：inflammation、RNA-seq
• 📝 描述：Contributors : Janel LeBelle ; Harley Kornblum ; Kaleab Tessema ; Riki Kawaguchi ; Lindsey DudleySeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusMaternal inflammatory response (MIR) during early gestation in mice induces a cascade of physiological and behavioral changes that have been associated with autism spectrum disorder (ASD). In a prior study and the current one, we find that mild MIR results in chronic systemic and brain inflammation, mTOR pathway activation, mild brain overgrowth followed by regionally specific volumetric changes, sensory processing dysregulation, and social and repetitive behavior abnormalities. Prior studies of rapamycin treatment in autism models have focused on chronic treatments that alter or prevent physical brain changes. Here, we have focused on the acute effects of rapamycin to uncover novel mechanisms of dysfunction related to mTOR pathway signaling. We find that within 2 hours, rapamycin treatment could rapidly rescue neuronal hyper-excitability, seizure susceptibility, functional network connectivity and brain community structure, repetitive behaviors, and sensory over-responsivity in adult offspring with persistent mild brain overgrowth. These CNS-mediated effects are also associated with alteration of the expression of several ASD-, ion channel-, and epilepsy-associated genes in the same time frame. Reduction of microglia with CSF1R inhibitors or inhibition of NADPH oxidase in young animals reduces the development of some of the behavioral phenotypes, but neither is as effective as acute mTOR inhibition. Our findings indicate that mTOR dysregulation in MIR offspring is a key contributor to various levels of brain dysfunction. However, we demonstrate that the adult MIR brain is also amenable to rapid normalization of these functional changes which results in the rescue of both core and comorbid ASD-like behaviors in adult animals without requiring long-term physical alterations to the brain. Restoring excitatory/inhibitory imbalance and sensory functional network modularity may therefore be important targets for therapeutically addressing both primary sensory and compensatory repetitive behavior phenotypes.
• 🔗 查看原文

8. GSE300984 单细胞多组学揭示病毒感染期间祖细胞 CD8 T 细胞和滤泡辅助性 CD4 T 细胞中共享的调控程序

• ✍️ 作者：未知作者
• 🏷️ 关键词：T cell、single-cell
• 📝 描述：Contributors : Sarah K Walker ; Joris van der Veeken ; Yuri PritykinSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusWe generated a new single-cell multiomic (scRNA-seq + scATAC-seq) dataset of CD4 and CD8 T cells responding to acute and chronic viral infection. To explore potential regulatory functions that might be shared by different populations of T cells, we generated a new single-cell multiomic (scRNA-seq + scATAC-seq) data for CD4 and CD8 T cells responding to acute and chronic viral infection. By integrating this new dataset with a compendium of 285 published bulk ATAC-seq datasets, we were able to identify all major T cell states, including naive, memory, effector, follicular helper (Tfh), regulatory, exhausted and progenitor populations, across both infection contexts. Archetypal analysis revealed regulatory programs that were driven by distinct transcription factors acting across multiple T cell subsets. Our work provides a broadly applicable framework and a valuable resource for dissecting transcriptional control mechanisms in adaptive immune responses.
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9. GSE325770：CDK7 和 CDK9 同时阻断可维持转录关闭并抑制癌症中的致癌依赖性

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、regex:onco(logy|logist|gene|genic)
• 📝 描述：Contributors : Catalan-Rabaneda Maria ; Castillo-Sanchez Jesus ; Sánchez-Belmonte Agustín ; Cubells Mariona ; Bonel Gloria C. ; Aliagas Elisabeth ; Hurtado Begoña ; Malumbres MarcosSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensTranscriptional cyclin-dependent kinases (CDKs) are attractive cancer targets owned to their critical role in the regulation of RNA polymerase II (RNAPII) to maintain oncogenic gene-expression programs. CDK7 supports transcriptional initiation and promoter escape, whereas CDK9 promotes productive elongation. Because inhibition of a single node can be partially buffered by transcriptional plasticity, we tested whether co-targeting CDK7 and CDK9 enforces a deeper and more durable transcriptional shutdown with improved antitumor activity. By combining genetic and pharmacological perturbations across breast and ovarian cancer models, we found that dual CDK7–CDK9 knockout caused the strongest suppression of proliferation and nascent RNA synthesis, accompanied by greater loss of RNAPII phosphorylation and pronounced depletion of MYC and MCL1, compared with single knockouts. Pharmacological co-inhibition phenocopied these effects, producing rapid EU suppression that preceded decreases in EdU incorporation and cell number, preventing adaptation to single treatments and yielding deeper pathway inhibition than either monotherapy. In ovarian cancer models, combined inhibition similarly enhanced suppression of transcriptional output and growth relative to single agents, supporting generalizability across tumor contexts. RNA sequencing after short inhibitor exposures showed that combined CDK7/CDK9 inhibition induced a transcriptomic state distinct from either single agent, with broad downregulation of pathways linked to transcription and RNA processing, ribosome biogenesis, and growth-associated programs. Together, these data support CDK7/CDK9 co-targeting as a mechanistically grounded strategy to intensify and stabilize transcriptional inhibition in cancer, coupling proximal RNAPII control to depletion of short-lived oncogenic drivers and collapse of growth-promoting networks and providing a clear rationale for combinatorial therapeutic development.
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10. GSE311328 小鼠 LSK、LK 和总骨髓细胞的单细胞 RNA 测序数据

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq、single-cell
• 📝 描述：Contributors : Sina Stäble ; Maximilian Schönung ; Mark Hartmann ; Mariam Hakobyan ; Stephen Krämer ; Oliver Mücke ; Simon Haas ; Jan-Philipp Mallm ; Karsten Rippe ; Matthias Schlesner ; Michael D Milsom ; Christoph Plass ; Daniel B LipkaSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculus10x scRNA-seq data broadly covering the murine hematopoietic system through three tiers: LSK, LK and total bone marrow.
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1. SCOTCH——通过长读长单细胞RNA测序进行基因表达的同源异构体水平表征

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing、single-cell
• 📝 描述：RNA sequencing with SCOTCH improves isoform-level analysis from long-read single-cell data, helping reveal cell-type-specific transcript diversity and novel RNA isoforms
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2. 利用单细胞RNA测序追踪早期心脏再生

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing、single-cell
• 📝 描述：RNA sequencing with metabolic labeling reveals early immune cell responses that shape zebrafish heart regeneration and may guide future cardiac repair strategies…
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3. 基于单细胞RNA测序图谱的组织动力学推断的统计分析

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing、single-cell
• 📝 描述：As a research assistant, you will work on a focused, well-scoped project with a clear scientific goal: bringing a single-cell tissue-dynamics analysis to publication in a leading scientific journal…
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• GSE310110 CD38⁺ 内皮重塑定义了快速进展的口腔炎症中空间多样化的血管病变程序
• GSE301461 IDH1-R132H 通过促进病毒进入和免疫激活增强溶瘤性 HSV-1 疗法在胶质瘤中的疗效
• GSE224790 维生素 C 通过 DNA 去甲基化对 T 细胞进行表观遗传调控 [ATAC-Seq]
• GSE224402 维生素C通过DNA去甲基化调控T细胞的表观遗传[体外刺激RNA测序]
• GSE224374 维生素 C 通过 DNA 去甲基化对 T 细胞进行表观遗传调控 [RNAseq Tet]
• GSE224373 维生素 C 通过 DNA 去甲基化对 T 细胞进行表观遗传调控 [RNAseq Gulo]
• GSE223985 维生素 C 通过 DNA 去甲基化对 T 细胞进行表观遗传调控 [scRNA]
• GSE210589 两个 MADS-box 转录因子介导番茄果实成熟的表观遗传控制 [RNA-seq]
• GSE210588 两个 MADS-box 转录因子介导番茄果实成熟的表观遗传控制 [ChIP-seq]
• GSE329991 干扰素-γ驱动的髓系炎症特征定义了免疫检查点抑制剂相关性心肌炎的糖皮质激素抵抗
• GSE329902 β-羟基丁酸通过组蛋白β-羟基丁酰化增强线粒体能量代谢
• GSE330399 BTK抑制剂和降解剂泛耐药性的分子和结构基础
• GSE330266 肝细胞 Hedgehog 信号通路调控铁死亡以缓解衰老相关的器官功能障碍
• GSE330182 肿瘤抑制因子 Tip60 响应微生物群抑制 TOR 信号传导，从而促进自噬和肠细胞分化 [RNAseq_Tip60]
• GSE328222 急性雷帕霉素治疗揭示了母体炎症小鼠模型中功能障碍的新机制
• GSE325455 肿瘤抑制因子Tip60通过抑制TOR信号通路响应肠道菌群，促进自噬和肠细胞分化
• GSE318030 优化的细胞核分离和 snRNA-seq 揭示了儿科患者 MOGHE 脑组织中少突胶质细胞通路失调。
• GSE318528 非酶促RNA糖基化将代谢应激与核糖毒性应激反应和β细胞功能障碍联系起来
• GSE308014 TREM1驱动的反馈回路增强炎症性肠病中中性粒细胞介导的炎症反应
• GSE261456 维生素 C 通过 DNA 去甲基化对 T 细胞进行表观遗传调控 [WGBS-Tn-Aged]
• GSE261372 维生素 C 通过 DNA 去甲基化对 T 细胞进行表观遗传调控 [CutRun-TCF7TET2]
• GSE225325 维生素 C 通过 DNA 去甲基化对 T 细胞进行表观遗传调控 [RNA Slc23a2KO]
• GSE224792 维生素 C 通过 DNA 去甲基化对 T 细胞进行表观遗传调控 [Cut & Tag]
• GSE224542 维生素 C 通过 DNA 去甲基化对 T 细胞进行表观遗传调控 [Slc23a2_WGBS]
• GSE224541 维生素 C 通过 DNA 去甲基化对 T 细胞进行表观遗传调控 [Gulo_WGBS]
• GSE224540 维生素 C 通过 DNA 去甲基化对 T 细胞进行表观遗传调控 [TET_WGBS]
• GSE224376 维生素C通过DNA去甲基化调控T细胞的表观遗传
• GSE210590 两个MADS-box转录因子介导番茄果实成熟的表观遗传调控
• GSE210587 两个 MADS-box 转录因子介导番茄果实成熟的表观遗传控制 [亚硫酸氢盐测序]
• GSE329936 混合转录组组装揭示果蝇血细胞中的编码和非编码图谱
• GSE329909 利用小鼠多能干细胞模拟组织驻留巨噬细胞发育
• GSE319464 SRR2KO 的 ATAC-seq
• GSE319463 SRR2KO 的 RNA-seq