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1. ⭐ GSE311362 静止肿瘤细胞塑造胰腺导管腺癌的免疫抑制微环境 [空间转录组学]

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributors : Bryan McClellan ; Quiju Wang ; William MatsuiSeries Type : OtherOrganism : Mus musculusImmunotherapy, including chimeric antigen receptor (CAR) T-cell therapy, has limited activity in pancreatic ductal adenocarcinoma (PDAC). Using orthotopic PDAC mouse models, we identified a rare population of quiescent PDAC cells that increases after CAR-T cell therapy and exhibits relatively higher clonogenic growth and self-renewal potential than bulk tumor cells. These quiescent cells express high levels of Epiregulin (EREG), a secreted ligand for EGFR and ErbB4, and induce an immunosuppressive tumor microenvironment by increasing the frequency of ErbB4-expressing tumor-associated macrophages. Silencing EREG expression increased the sensitivity of both quiescent cells and tumors to CAR-T cells and improved relapse rates and overall survival. These findings demonstrate that rare quiescent tumor cells can modulate the tumor microenvironment in PDAC and suggest that EREG inhibition may enhance the efficacy of adoptive immunotherapeutic approaches in this disease.
• 🔗 查看原文

2. ⭐ GSE317356 单细胞多组学方法定义了从胚胎到成体神经干细胞的渐进的、空间调控的表观遗传和转录转变[scRNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：single-cell、scRNA、spatially、epigenetic
• 📝 描述：Contributors : Beatrix S Wang ; Konstantina Karamboulas ; Nareh Tahmasian ; Daniel J Dennis ; David R Kaplan ; Freda D MillerSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusHere, we ask how adult neural stem cells (NSCs) arise developmentally, focusing on murine cortical precursors that generate excitatory neurons embryonically and interneurons and glial cells postnatally. Using complementary single-cell spatial, transcriptomic, and epigenomic approaches, we show that postnatal NSC state acquisition involves a gradual transcriptional and epigenetic shift in the entire embryonic cortical precursor cell population and identify a distinct transition precursor state at E17/18 when both embryonic and the first postnatal progeny are being generated. Non-proliferative adult NSCs are also first seen at this transition timepoint, but they arise in a spatial domain distinct from that of the first postnatal progeny, indicating that NSC state acquisition is not a necessary prelude to the switch in cell genesis. These findings support a gradual epigenetically-continuous model for the transition from developing cortical precursors to NSCs and show that this is spatially separable from the transition to generating postnatal cell types.
• 🔗 查看原文

3. ⭐ GSE272886 体内双敲除 CAR-T 筛选鉴定出增强抗肿瘤免疫的协同基因对 [scRNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、immunity、scRNA
• 📝 描述：Contributors : Paul Renauer ; Liqun Zhou ; Sidi ChenSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensChimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematological malignancies. However, its efficacy against solid tumors is hindered by multifaceted negative regulatory mechanisms intrinsic to T cells. Although single gene screens have been performed in T cells, such studies cannot provide causality for the complex genetic interactions governing T cell function. To systematically discover genetic interactions that are critical for CAR-T cell’s anti-tumor immunity, here, we perform a high-throughput in vivo double-knockout (DKO) CRISPR screen in human CAR-T cells and identify multiple DKO gene pairs that are both effective and synergistic. All five top-scoring DKO hits are validated to promote CAR-T cell activation, cytotoxicity, degranulation, effector cytokine production, and memory formation, and reduce exhaustion. Mechanistically, these DKOs enhance calcium influx, phospho-ERK, NF-κB and NFAT/AP-1 signaling. Among these hits, NR4A1_SOCS3 DKO has multiple favorable immunological features and showcases the most robust phenotypes. NR4A1_SOCS3 DKO CAR-T cells show potent in vivo anti-tumor efficacy and markedly enhanced infiltration as compared to both single gene knockouts, without increase in safety risk. Whole-transcriptome profiling and single cell RNA sequencing of tumor-infiltrating CAR-T cells reveal that NR4A1_SOCS3 DKO specifically enhanced metabolic fitness of CAR-T cells, rendering them exceptionally potent in long-term tumor control in an orthotopic model, superior to both single gene knockouts and the PD1_CTLA4 dual-checkpoint DKO benchmark. These data together demonstrate the efficacy of high-throughput DKO screening to rapidly uncover critical genetic interactions within T cells, and discover NR4A1_SOCS3 as promising joint intracellular checkpoints to engineer high-performance CAR-T therapies against solid tumors.
• 🔗 查看原文

4. ⭐ GSE272885 体内双敲除 CAR-T 筛选鉴定出增强抗肿瘤免疫的协同基因对 [bulk RNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、immunity、RNA-seq
• 📝 描述：Contributors : Paul Renauer ; Liqun Zhou ; Sidi ChenSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensChimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematological malignancies. However, its efficacy against solid tumors is hindered by multifaceted negative regulatory mechanisms intrinsic to T cells. Although single gene screens have been performed in T cells, such studies cannot provide causality for the complex genetic interactions governing T cell function. To systematically discover genetic interactions that are critical for CAR-T cell’s anti-tumor immunity, here, we perform a high-throughput in vivo double-knockout (DKO) CRISPR screen in human CAR-T cells and identify multiple DKO gene pairs that are both effective and synergistic. All five top-scoring DKO hits are validated to promote CAR-T cell activation, cytotoxicity, degranulation, effector cytokine production, and memory formation, and reduce exhaustion. Mechanistically, these DKOs enhance calcium influx, phospho-ERK, NF-κB and NFAT/AP-1 signaling. Among these hits, NR4A1_SOCS3 DKO has multiple favorable immunological features and showcases the most robust phenotypes. NR4A1_SOCS3 DKO CAR-T cells show potent in vivo anti-tumor efficacy and markedly enhanced infiltration as compared to both single gene knockouts, without increase in safety risk. Whole-transcriptome profiling and single cell RNA sequencing of tumor-infiltrating CAR-T cells reveal that NR4A1_SOCS3 DKO specifically enhanced metabolic fitness of CAR-T cells, rendering them exceptionally potent in long-term tumor control in an orthotopic model, superior to both single gene knockouts and the PD1_CTLA4 dual-checkpoint DKO benchmark. These data together demonstrate the efficacy of high-throughput DKO screening to rapidly uncover critical genetic interactions within T cells, and discover NR4A1_SOCS3 as promising joint intracellular checkpoints to engineer high-performance CAR-T therapies against solid tumors.
• 🔗 查看原文

5. ⭐ GSE291238 SUV39H1/2 介导的 H3K9me3 限制了 TE 诱导的急性髓系白血病免疫反应 (ATAC-Seq)

• ✍️ 作者：未知作者
• 🏷️ 关键词：leukemia、immune、ATAC-seq
• 📝 描述：Contributors : Feng Yue ; Josiah Hiu-yuen Wong ; Shaojun Yu ; Yang Cheng ; Hengqiang Zhao ; Xintong Chen ; Yihao Fu ; Ping Wang ; Huijue Lyu ; Alok SwaroopSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensHistone 3 Lysine 9 tri-methylation (H3K9me3) is a heterochromatin-associated histone mark deposited broadly across the genome and its regulation is required in normal hematopoiesis. Furthermore, H3K9me3 has been linked with 3D genome organization. However, in the context of acute myeloid leukemia (AML), the regulation of H3K9me3 and its function in 3D genome architecture remained understudied. In this study, through systematic Knockdowns and Knockouts, we identified SUV39H1 and by part its paralogue SUV39H2 as the major H3K9me3 depositors in AML. We demonstrated the role of SUV39H1/2 in establishing global H3K9me3 levels in AML cells and showed H3K9me3 depletion upon SUV39H1/2 Knockout preferentially occurred at sub-megabase level broad peaks and in GC poor regions. Loss of SUV39H1/2-mediated H3K9me3 poised AML cells towards monocyte/macrophage differentiation, induced TE re-activation and interferon response activation, and reduced AML cell growth and clonogenicity in vitro. Analysis of higher-order chromatin architecture reveals that while SUV39H1/2-mediated H3K9me3 is associated with a small fraction of larger chromatin structures, loss of SUV39H1/2 drives concomitant increase of H3K27me3 at B compartments. Taken together, our findings characterize the regulation of SUV39H1/2-mediated H3K9me3 and reveal its role in leukemogenesis and higher-order chromatin structure.
• 🔗 查看原文

6. ⭐ GSE285125 SUV39H1/2 介导的 H3K9me3 限制了 TE 诱导的急性髓系白血病免疫反应 [RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：leukemia、immune、RNA-seq
• 📝 描述：Contributors : Yue Feng ; Wong Josiah Hiu-yuen ; Yu Shaojun ; Cheng Yang ; Zhao Hengqiang ; Chen Xintong ; Fu Yihao ; Wang Ping ; Lyu Huijue ; Swaroop AlokSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensHistone 3 Lysine 9 tri-methylation (H3K9me3) is a heterochromatin-associated histone mark deposited broadly across the genome and its regulation is required in normal hematopoiesis. Furthermore, H3K9me3 has been linked with 3D genome organization. However, in the context of acute myeloid leukemia (AML), the regulation of H3K9me3 and its function in 3D genome architecture remained understudied. In this study, through systematic Knockdowns and Knockouts, we identified SUV39H1 and by part its paralogue SUV39H2 as the major H3K9me3 depositors in AML. We demonstrated the role of SUV39H1/2 in establishing global H3K9me3 levels in AML cells and showed H3K9me3 depletion upon SUV39H1/2 Knockout preferentially occurred at sub-megabase level broad peaks and in GC poor regions. Loss of SUV39H1/2-mediated H3K9me3 poised AML cells towards monocyte/macrophage differentiation, induced TE re-activation and interferon response activation, and reduced AML cell growth and clonogenicity in vitro. Analysis of higher-order chromatin architecture reveals that while SUV39H1/2-mediated H3K9me3 is associated with a small fraction of larger chromatin structures, loss of SUV39H1/2 drives concomitant increase of H3K27me3 at B compartments. Taken together, our findings characterize the regulation of SUV39H1/2-mediated H3K9me3 and reveal its role in leukemogenesis and higher-order chromatin structure.
• 🔗 查看原文

7. ⭐ GSE285122 SUV39H1/2 介导的 H3K9me3 限制了 TE 诱导的急性髓系白血病免疫反应 [ChIP-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：leukemia、immune、ChIP-seq
• 📝 描述：Contributors : Feng Yue ; Josiah Hiu-yuen Wong ; Shaojun Yu ; Yang Cheng ; Hengqiang Zhao ; Xintong Chen ; Yihao Fu ; Ping Wang ; Huijue Lyu ; Alok SwaroopSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensHistone 3 Lysine 9 tri-methylation (H3K9me3) is a heterochromatin-associated histone mark deposited broadly across the genome and its regulation is required in normal hematopoiesis. Furthermore, H3K9me3 has been linked with 3D genome organization. However, in the context of acute myeloid leukemia (AML), the regulation of H3K9me3 and its function in 3D genome architecture remained understudied. In this study, through systematic Knockdowns and Knockouts, we identified SUV39H1 and by part its paralogue SUV39H2 as the major H3K9me3 depositors in AML. We demonstrated the role of SUV39H1/2 in establishing global H3K9me3 levels in AML cells and showed H3K9me3 depletion upon SUV39H1/2 Knockout preferentially occurred at sub-megabase level broad peaks and in GC poor regions. Loss of SUV39H1/2-mediated H3K9me3 poised AML cells towards monocyte/macrophage differentiation, induced TE re-activation and interferon response activation, and reduced AML cell growth and clonogenicity in vitro. Analysis of higher-order chromatin architecture reveals that while SUV39H1/2-mediated H3K9me3 is associated with a small fraction of larger chromatin structures, loss of SUV39H1/2 drives concomitant increase of H3K27me3 at B compartments. Taken together, our findings characterize the regulation of SUV39H1/2-mediated H3K9me3 and reveal its role in leukemogenesis and higher-order chromatin structure.
• 🔗 查看原文

8. ⭐ GSE318202 单细胞多组学方法定义了从胚胎到成体神经干细胞的渐进的、空间调控的表观遗传和转录转变 [Xenium]

• ✍️ 作者：未知作者
• 🏷️ 关键词：single-cell、spatially、epigenetic
• 📝 描述：Contributors : Beatrix S Wang ; Konstantina Karamboulas ; Nareh Tahmasian ; Daniel J Dennis ; David R Kaplan ; Freda D MillerSeries Type : OtherOrganism : Mus musculusHere, we ask how adult neural stem cells (NSCs) arise developmentally, focusing on murine cortical precursors that generate excitatory neurons embryonically and interneurons and glial cells postnatally. Using complementary single-cell spatial, transcriptomic, and epigenomic approaches, we show that postnatal NSC state acquisition involves a gradual transcriptional and epigenetic shift in the entire embryonic cortical precursor cell population and identify a distinct transition precursor state at E17/18 when both embryonic and the first postnatal progeny are being generated. Non-proliferative adult NSCs are also first seen at this transition timepoint, but they arise in a spatial domain distinct from that of the first postnatal progeny, indicating that NSC state acquisition is not a necessary prelude to the switch in cell genesis. These findings support a gradual epigenetically-continuous model for the transition from developing cortical precursors to NSCs and show that this is spatially separable from the transition to generating postnatal cell types.
• 🔗 查看原文

9. ⭐ GSE317357 单细胞多组学方法定义了从胚胎到成体神经干细胞的渐进的、空间调控的表观遗传和转录转变[多组学]

• ✍️ 作者：未知作者
• 🏷️ 关键词：single-cell、spatially、epigenetic
• 📝 描述：Contributors : Beatrix S Wang ; Konstantina Karamboulas ; Nareh Tahmasian ; Daniel J Dennis ; David R Kaplan ; Freda D MillerSeries Type : Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencingOrganism : Mus musculusHere, we ask how adult neural stem cells (NSCs) arise developmentally, focusing on murine cortical precursors that generate excitatory neurons embryonically and interneurons and glial cells postnatally. Using complementary single-cell spatial, transcriptomic, and epigenomic approaches, we show that postnatal NSC state acquisition involves a gradual transcriptional and epigenetic shift in the entire embryonic cortical precursor cell population and identify a distinct transition precursor state at E17/18 when both embryonic and the first postnatal progeny are being generated. Non-proliferative adult NSCs are also first seen at this transition timepoint, but they arise in a spatial domain distinct from that of the first postnatal progeny, indicating that NSC state acquisition is not a necessary prelude to the switch in cell genesis. These findings support a gradual epigenetically-continuous model for the transition from developing cortical precursors to NSCs and show that this is spatially separable from the transition to generating postnatal cell types.
• 🔗 查看原文

10. GSE318722 10X 基因组多组分析 (GEX + ATAC) 产前雄激素化和对照青春期前雌性小鼠下丘脑视前区。

• ✍️ 作者：未知作者
• 🏷️ 关键词：10x、genomics
• 📝 描述：Contributors : Laura L Burger ; Rujuta M Chikodikar ; Suzanne M MoenterSeries Type : Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencingOrganism : Mus musculusPolycystic ovary syndrome (PCOS) is the most common cause of infertility in women. The etiology of PCOS is not well understood. Both genetics and early life exposures are considered contributing factors. Women with PCOS have elevated androgens, potentially exposing female offspring to high androgens in utero. Daughters of women with PCOS are at increased risk of developing this disorder. Prenatal androgenization (PNA) of several species, including mice, recapitulates many phenotypes observed in PCOS. Adult female PNA mice exhibit elevated luteinizing hormone (LH) levels and increased gonadotropin-releasing hormone (GnRH) neuron pulse frequency. These changes in GnRH neurons emerge during the pubertal transition. We utilized the 10X Genomics Multiome (gene expression and ATAC-seq) assay to investigate changes in both gene expression and chromatin accessibility in the hypothalamic preoptic area of prepubertal (postnatal day 21) control and PNA females. Through analysis of ~51,000 cells across 34 cell populations, we identified cell-type-specific chromatin remodeling in response to prenatal androgen exposure, despite the absence of coordinated transcriptional changes at postnatal day 21, suggesting that critical developmental programming occurs earlier with persistent epigenetic consequences.
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1. 以Bioconductor为中心的空间组学和图像衍生数据黑客马拉松

• ✍️ 作者：未知作者
• 🏷️ 关键词：spatial、Bioconductor
• 📝 描述：A Bioconductor-centric hackathon dedicated to spatial omics was organized by members of the Bioconductor community – Davide Risso (University of Padua, Italy), Helena Crowell (CNAG Barcelona, Spain), and Wolfgang Huber (EMBL) – on 19-22 April on… Continue reading: Bioconductor-centric hackathon on spatial omics and image-derived data
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• GSE311084 单细胞 RNA 测序揭示股骨头坏死中软骨细胞的异质性和纤维软骨转变
• GSE285123 SUV39H1/2 介导的 H3K9me3 限制了 TE 诱导的急性髓系白血病免疫反应 [HiC]
• GSE284008 RNA 测序数据来自小鼠肾脏，用于识别肾脏中对 VNS 和/或巨噬细胞特异性 Notch2 缺失有反应的候选因子。
• GSE279941 髓系细胞中Egfr的缺失可对抗CRC中的免疫抑制性肿瘤微环境
• GSE272887 体内双敲除 CAR-T 筛选鉴定出增强抗肿瘤免疫的协同基因对。
• GSE272884 体内双敲除 CAR-T 筛选鉴定出增强抗肿瘤免疫的协同基因对 [crispr_screen]
• GSE326045 整合转录组-代谢组分析揭示辣椒果实中可溶性固形物积累的调控网络
• GSE311363 静止肿瘤细胞塑造胰腺导管腺癌的免疫抑制微环境 [RNA-Seq]
• GSE285857 突变型 KRAS 驱动的选择性 mRNA 翻译揭示了癌症的机制和治疗弱点
• GSE299182 USP43 通过稳定膀胱癌中的 E2F1 来调节胆固醇稳态，从而促进吉西他滨耐药性
• GSE309906 类风湿性关节炎患者和健康对照者干细胞样记忆T (Tscm) 细胞的单细胞RNA测序
• GSE206078 ZNF512B 通过调控区域保护基因组完整性来抑制 SASP 和炎症
• 对 vtRNA 敲除的 HEK293T 细胞系进行 GSE335700 RNA 测序
• GSE334867 人类造血干细胞克隆在随机多样化和细胞因子诱导分化之间取得平衡
• GSE335729 铜绿假单胞菌 LysR 型转录调节因子 PA3321 对生物膜的形成至关重要，并影响毒力和致病性 [ChIP-seq]
• GSE335716 高分辨率转录组分析揭示了古菌病毒 SSV1 的多层动态转录结构
• GSE329552 非人灵长类动物 LIBRA-Seq 加速了接种 HIV-1 疫苗的恒河猴体内中和抗体的发现
• GSE325334 TRIM5a抑制波瓦桑病毒复制促进病毒逃避免疫反应
• GSE302775 FABP4结合的癌细胞通过PKC-mitoROS信号通路表现出侵袭性表型
• GSE301500 瞬时 YAP/TAZ 抑制暴露晚期癌症的治疗弱点 [ATAC-seq]
• GSE301495 瞬时 YAP/TAZ 抑制暴露晚期癌症的治疗弱点 [scRNA-Seq 2]
• GSE301494 瞬时 YAP/TAZ 抑制暴露晚期癌症的治疗弱点 [scRNA-Seq 1]
• GSE301491 瞬时 YAP/TAZ 抑制暴露晚期癌症的治疗弱点 [RNA-Seq]
• GSE291186 小鼠关节炎中的紧急髓系造血导致树突状细胞发育和功能的细胞内在变化
• GSE335694 母体维生素C缺乏和遗传风险因素通过DNA甲基化失调导致先天性畸形。[CUT&Tag E8.5]
• GSE305671 分化动力学失调是克隆胎盘中 DNA 损伤修复的关键作用 [ChIP-Seq]
• GSE300281：TGF-β处理的AGPS敲除乳腺癌细胞的转录组分析
• GSE282876 不同的分化轨迹对 V2a 神经元的基因调控和功能产生持久影响 [批量 RNA 测序]
• GSE328808 α蛋白激酶3基因疗法可恢复小鼠和人类心肌病模型的心脏功能