详细内容（前10条）

1. ⭐ GSE275837 嵌合抗原受体-巨噬细胞外囊泡重编程免疫微环境用于癌症治疗 [scRNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、immune、macrophage、antigen、scRNA
• 📝 描述：Contributors : Minghe Zhang ; Peng Xia ; Yufeng YuanSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusImmunotherapy has become a new milestone in cancer treatment, with chimeric antigen receptor (CAR)-T cell therapy proven to be an effective method for treating hematologic malignancies. However, its efficacy in solid tumors remains limited. Macrophages, the most infiltrative innate immune cells in the tumor microenvironment, are being genetically engineered to express CARs, rapidly emerging as a promising new therapy for non-hematologic malignancies. Yet, CAR- Macrophages therapy is associated with unique acute toxicities and is susceptible to immunosuppressive mechanisms. Here, we propose using CAR macrophages-derived extracellular vesicles (CAR-MEVs) as an optimization of CAR-Ms therapy. Compared to CAR-Ms cells, CAR-MEVs exhibit lower toxicity and enhanced drug delivery capabilities. In an in vivo liver cancer model, CAR-MEVs administration proved safer than CAR-Ms therapy, reducing tumor burden and prolonging overall survival. In a humanized mouse model, CAR-MEVs further demonstrated the ability to induce a pro-inflammatory tumor microenvironment and enhance anti-tumor T cell activity. Mechanistically, CAR-MEVs target tumor cells, inducing immunogenic cell death (ICD) and subsequently leading to neutrophil infiltration in tumor tissues. We demonstrated that the anti-tumor effects of CAR-MEVs depend on neutrophils and are partially reliant on inducible nitric oxide synthase (iNOS). This study supports the potential of macrophage extracellular vesicles as a novel therapeutic approach for solid tumors.
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2. ⭐ GSE273952 GABA 促进 TLS 阳性肿瘤患者对免疫疗法的耐药性 [空间转录组学]

• ✍️ 作者：未知作者
• 🏷️ 关键词：regex:immuno(logy|therapy|suppression)、resistance、spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributors : Isaias Hernandez-Verdin ; Anne Calvez ; Antoine Bougoüin ; Cheng-Ming Sun ; Asmat Ullah ; Virgine Verkarre ; Yann-Alexandre Vano ; Lucile Vanhersecke ; Alban Bessede ; Jean-Philippe Guegan ; Antoine Italiano ; Stéphane Oudard ; Catherine Sautès-Fridman ; Wolf H FridmanSeries Type : OtherOrganism : Homo sapiensTertiary lymphoid structures (TLS) in the tumour microenvironment have been linked to positive clinical outcomes and responses to immune checkpoint inhibitors (ICI) in various cancers, including clear cell renal cell carcinoma (ccRCC) and soft tissue sarcoma (STS). However, a significant proportion of patients do not respond to ICI despite the presence of TLS. Our study unravels gamma-aminobutyric acid (GABA), a neurotransmission inhibitor, as a modulator of ICI resistance in TLS-positive tumours. By leveraging household and public multi-omic data, we demonstrated that GABA is upregulated in TLS-positive ccRCC and STS tumours from non-responders to ICI. In metastatic ccRCC, TLS from non-responders were distinguished from responders by a dysfunctional immune activation and a close proximity to GABA-producing proximal tubule-like tumour cells. The addition of a competitive inhibitor of GABA synthesis, 3-mercaptopropionic acid, significantly improved tumour control when compared to anti-PD1 alone when intra-tumourally injected in a mouse model of STS. Overall, our findings highlight GABA as a novel determinant of non-response to ICI in tumours harboring TLS, suggesting potential new approaches for patient stratification and personalized therapeutic strategies that could be applicable beyond metastatic ccRCC and STS.
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3. ⭐ GSE306606 多模态空间转录组学以单细胞分辨率揭示人类肝脏发育微环境

• ✍️ 作者：未知作者
• 🏷️ 关键词：single-cell、spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributor : Carolyn SangokoyaSeries Type : OtherOrganism : Homo sapiensA comprehensive understanding of the fetal liver niche during development offers a lens into a unique natural multifunctional multicellular environment. Here we use a spatial transcriptomic and histologic analysis approach to identify and histologically confirm RNA-based markers in human fetal liver tissue within a key developmental window in which the liver is a major site of hematopoiesis, just prior to the increased growth phase of the final trimester. Within this window, the fetal liver niche encompasses the unique coexistence of cells of both endodermal and mesenchymal origin with the unique environment fostering hematopoietic cell development as well as hepatocyte function. Single-cell resolution spatial imaging reveals epithelial, hematopoietic, endothelial, and stromal cell populations in shared cellular microenvironments. Here, our single-cell spatial transcriptomic and imaging approach enables, captures, and confirms the complex phenomena of ductal plate expression and CXCL12 homing to the hematopoietic stem cell niche (HSC) in the liver. An RNA-based understanding of the functional diversity and in situ spatial organization of the fetal liver niche is critical for adequate validation and authentication in recapitulating and re-engineering these regenerative environments in vitro.
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4. ⭐ GSE318757 SynNotch-iNOS CAR-巨噬细胞重塑肿瘤免疫微环境，并通过CD4+ T细胞依赖性机制发挥抗肿瘤功效

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、immune、T cell
• 📝 描述：Contributors : Yuling Hong ; Buyun Dang ; Shih-Chin ChengSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusBackground: Chimeric antigen receptor T-cell (CAR-T) therapy shows limited efficacy against solid tumors due to the immunosuppressive tumor microenvironment (TIME). Macrophages possess superior infiltration capabilities, yet their therapeutic potential remains under-realized. Methods: We engineered a synNotch-iNOS CAR-macrophage (CAR iNOS-M) that releases nitric oxide (NO) upon CD19 recognition. Its efficacy was evaluated in syngeneic, immunocompetent murine models of metastatic melanoma. Results: CAR iNOS-M therapy effectively reprogrammed the pulmonary TIME, inducing potent antitumor responses independent of CD8+ T cells but strictly dependent on CD4+ T cells. Mechanistically, CAR iNOS-M treatment led to a significant reduction in pro-tumorigenic lung interstitial macrophages (IMs), subsequently decreasing platelet factor 4 (PF4) levels. This disruption of the PF4 signaling axis inhibited the polarization of immunosuppressive Th1-Tregs, alleviating T-cell exhaustion. Conclusions: This study delineates a novel indirect mechanism for CAR-M, shifting the focus from direct phagocytosis to strategic TIME remodeling, providing a foundation for treating solid tumors.
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5. ⭐ GSE318979 利用 LAG3 靶向的白细胞介素-2 靶向肿瘤特异性 T 细胞可防止 T 细胞耗竭并重新激活抗肿瘤免疫力

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、immunity、T cell
• 📝 描述：Contributors : Xiaohong Yu ; Huiping LiaoSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusLAG3 is a critical inhibitory receptor that is highly enriched on exhausted T cells within the tumor microenvironment (TME), where it functions as a key driver of T cell exhaustion-an archetypal barrier to robust antitumor immunity. In a colon cancer model, we identified that LAG3+CD8+ tumor-infiltrating lymphocytes (TILs) constitute the predominant tumor-specific T cells but exhibit defective IL2 signaling. To address whether exogenous IL2 replenishment unpins their dysfunction, we engineered LAG3-LaIL2 (low-affinity IL2), a fusion protein delivering IL2 selectively to LAG3+CD8+ TILs. LAG3-LaIL2 expanded pre-exhausted tumor-specific CD8+ T cells, reprogrammed their exhaustion trajectory toward an intermediate effector state, and prevented terminal exhaustion, leading to tumor regression and prolonged survival in mice. Mechanistically, LAG3-LaIL2 restored IL2R-JAK3-STAT5 signaling by upregulating the high-affinity IL2 receptor subunit CD122, thereby rejuvenating TIL functionality. Furthermore, LAG3-LaIL2 amplified tumor-specific effector and memory T cells in draining lymph nodes, enabling systemic antitumor immunity against distal tumors and preventing tumor recurrence. Collectively, our findings validate LAG3-LaIL2 as a precision immunotherapeutic agent that specifically targets exhausted TILs, concomitantly enhancing therapeutic efficacy and safety by restricting IL2 exposure to non-target cells. This strategy provides a translatable approach to overcoming T cell exhaustion in solid tumors, offering a promising avenue to improve clinical outcomes for cancer patients
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6. ⭐ GSE304059：RBX1促进肾透明细胞癌侵袭、免疫抑制和舒尼替尼耐药的机制研究

• ✍️ 作者：未知作者
• 🏷️ 关键词：carcinoma、immune、resistance
• 📝 描述：Contributors : Yi Yu ; shaochao Zhan ; Yuchen Li ; Zhaohui Guo ; Ting Li ; Chengjian Xie ; Tao YangSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensClear cell renal cell carcinoma (ccRCC) often exhibits drug resistance, highlight_x0002_ing the need to identify novel therapeutic targets. RING box protein 1 (RBX1), an E3 ubiquitin ligase associated with tumor progression, has an unclear role in ccRCC. This study investigated the clinical significance, molecular mech_x0002_anisms, and role of RBX1 in treatment resistance through multi-omics and functional analyses. Analysis of The Cancer Genome Atlas (TCGA) data revealed that RBX1 is overexpressed in ccRCC and is associated with advanced dis_x0002_ease stages and poor prognosis. Functional enrichment studies linked RBX1 to processes such as cytoskeletal remodeling,extracellular matrix deposition, and lipid metabolism disorders.Additionally, tumors with high RBX1 expression exhibit an immunosuppressive microenvironment characterized by increased reg_x0002_ulatory T cells (Tregs) and elevated expression of immune checkpoint markers (LAG3/Galectin-9). In vitro experiments confirmed that RBX1 promotes ccRCC proliferation, migration, and invasion while conferring resistance to the standard targeted therapy drug sunitinib. Our findings suggest that RBX1 may serve as a key driver of ccRCC invasiveness and immune suppression. These discoveries indicate that RBX1 has the potential to become a prognostic biomarker and a target for precision therapy in advanced ccRCC.
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7. ⭐ GSE282444 炎症性肠病中肠上皮细胞的表观遗传记忆 [RNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq、epigenetic、regex:intestin(e|al)
• 📝 描述：Contributors : Brooke R Druliner ; Feda HamdanSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensThe pathogenesis of Inflammatory Bowel Disease (IBD) is a multifactorial process characterized by inflammation and damage to the intestinal barrier, which is made up of intestinal epithelial cells (IECs). Since IBD is a remitting and relapsing disease, we postulated that epigenetic memory exists in IECs following an inflammatory encounter. The objective of this study was to uncover the mechanisms of a retained altered IEC epigenetic landscape in the context of IBD. We have generated adult stem cell organoids (containing all epithelial cell lineages) from patients with Ulcerative Colitis (UC); two organoid lines per patient were propagated: 1) from a site of active inflammation and from the same patient, and 2) a never inflamed region. We performed Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and bulk RNA-seq on each organoid line. Established bioinformatic pipelines were used to determine significantly different chromatin accessibility and differentially expressed genes. Functional significance of the open chromatin regions was assessed by pathway and motif analysis. Treatment with TNF-alpha (10 and 100ng/ml) for 24 hours on the organoids was performed to determine re-activation of pro-inflammatory genes. This study shows for the first time that epithelial cells derived from organoids of IBD patients retain an epigenetic memory of the prior inflammatory state.
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8. ⭐ GSE282442 炎症性肠病中肠上皮细胞的表观遗传记忆 [ATAC-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：ATAC-seq、epigenetic、regex:intestin(e|al)
• 📝 描述：Contributors : Brooke R Druliner ; Feda HamdanSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensThe pathogenesis of Inflammatory Bowel Disease (IBD) is a multifactorial process characterized by inflammation and damage to the intestinal barrier, which is made up of intestinal epithelial cells (IECs). Since IBD is a remitting and relapsing disease, we postulated that epigenetic memory exists in IECs following an inflammatory encounter. The objective of this study was to uncover the mechanisms of a retained altered IEC epigenetic landscape in the context of IBD. We have generated adult stem cell organoids (containing all epithelial cell lineages) from patients with Ulcerative Colitis (UC); two organoid lines per patient were propagated: 1) from a site of active inflammation and from the same patient, and 2) a never inflamed region. We performed Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and bulk RNA-seq on each organoid line. Established bioinformatic pipelines were used to determine significantly different chromatin accessibility and differentially expressed genes. Functional significance of the open chromatin regions was assessed by pathway and motif analysis. Treatment with TNF-alpha (10 and 100ng/ml) for 24 hours on the organoids was performed to determine re-activation of pro-inflammatory genes. This study shows for the first time that epithelial cells derived from organoids of IBD patients retain an epigenetic memory of the prior inflammatory state.
• 🔗 查看原文

9. ⭐ GSE273829 GABA 促进 TLS 阳性肿瘤患者对免疫疗法的耐药性 [RNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：regex:immuno(logy|therapy|suppression)、resistance、RNA-seq
• 📝 描述：Contributors : Isaias Hernandez-Verdin ; Anne Calvez ; Antoine Bougoüin ; Cheng-Ming Sun ; Asmat Ullah ; Virgine Verkarre ; Yann-Alexandre Vano ; Lucile Vanhersecke ; Alban Bessede ; Jean-Philippe Guegan ; Antoine Italiano ; Stéphane Oudard ; Catherine Sautès-Fridman ; Wolf H FridmanSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensTertiary lymphoid structures (TLS) in the tumour microenvironment have been linked to positive clinical outcomes and responses to immune checkpoint inhibitors (ICI) in various cancers, including clear cell renal cell carcinoma (ccRCC) and soft tissue sarcoma (STS). However, a significant proportion of patients do not respond to ICI despite the presence of TLS. Our study unravels gamma-aminobutyric acid (GABA), a neurotransmission inhibitor, as a modulator of ICI resistance in TLS-positive tumours. By leveraging household and public multi-omic data, we demonstrated that GABA is upregulated in TLS-positive ccRCC and STS tumours from non-responders to ICI. In metastatic ccRCC, TLS from non-responders were distinguished from responders by a dysfunctional immune activation and a close proximity to GABA-producing proximal tubule-like tumour cells. The addition of a competitive inhibitor of GABA synthesis, 3-mercaptopropionic acid, significantly improved tumour control when compared to anti-PD1 alone when intra-tumourally injected in a mouse model of STS. Overall, our findings highlight GABA as a novel determinant of non-response to ICI in tumours harboring TLS, suggesting potential new approaches for patient stratification and personalized therapeutic strategies that could be applicable beyond metastatic ccRCC and STS.
• 🔗 查看原文

10. GSE321762 血管平滑肌细胞状态轨迹介导冠心病风险的分子机制[scRNA-seq 和 scATAC-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：scRNA、scATAC
• 📝 描述：Contributors : Daniel Y Li ; Thomas QuertermousSeries Type : Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencingOrganism : Mus musculusVascular smooth muscle cells contribute to heritable coronary artery disease risk and undergo complex transitions to multiple disease-related phenotypes. To investigate the genetic basis of these trajectories, we develop a dense timecourse single cell transcriptomic and epigenetic map of atherosclerosis in a murine disease model accompanied by high-plex in situ spatial data. Using temporal data and probabilistic fate modeling, we identify key transcription factors that drive cell state changes through a combination of network-based prioritization and in silico transcription factor perturbation. Parallel knockout studies of validated coronary artery disease gene Tcf21 uncover its molecular mechanisms in smooth muscle cell transition, due in part to a role regulating the transition of smooth muscle cells in the secondary heart field. Integrating the murine atlas with human coronary artery disease genetics pinpoint smooth muscle cell phenotypes that mediate disease risk, highlighting causal disease mechanisms. Together, these studies resolve atherosclerosis trajectories at single cell resolution and identify genetic causal transcriptomic and epigenomic mechanisms of coronary artery disease risk.
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1. SUM-seq——单细胞超高通量多重染色质可及性和基因表达测序

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing、single-cell
• 📝 描述：SUM-seq enables scalable single cell chromatin accessibility and RNA sequencing, supporting high throughput multimodal profiling for large atlas projects and regulatory network analysis…
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2. 聊天机器人简化了RNA测序数据分析

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing
• 📝 描述：REDAC enables accessible RNA sequencing expression analysis through natural language queries, automated normalization and differential testing, and AI guided pathway…
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3. 美国心脏协会警告称，到2050年，60%的美国女性将患有心血管疾病。

• ✍️ 作者：未知作者
• 🏷️ 关键词：cardiovascular
• 📝 描述：Heart disease is on track to tighten its grip on American women. New projections from the American Heart Association warn that over the next 25 years, cardiovascular disease will rise sharply, driven largely by a surge in high blood pressure, diabetes, and obesity. By 2050, nearly 60% of women in the U.S. could have high blood pressure, and close to one in three women ages 22 to 44 may already be living with some form of heart disease.
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4. 科学家发现一种微生物，它打破了遗传密码的一条基本规则。

• ✍️ 作者：未知作者
• 🏷️ 关键词：regex:micro(b|be|bial|organism)
• 📝 描述：Scientists at UC Berkeley have discovered a microbe that bends one of biology’s most sacred rules. Instead of treating a specific three-letter DNA code as a clear “stop” signal, this methane-producing archaeon sometimes reads it as a green light—adding an unusual amino acid and continuing to build the protein. The result is a kind of genetic coin flip: two different proteins can emerge from the same code, influenced partly by environmental conditions.
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• GSE320214 生酮饮食使胰腺癌对谷氨酰胺代谢抑制剂更敏感
• GSE314386 C15ORF48 对基底细胞亚群中线粒体 ROS 的调控导致三阴性乳腺癌化疗耐药
• GSE322475 乳酸和组蛋白 H3K18 乳酸化与视网膜基因表达的代谢控制相关 [explant_RNA-seq 2]
• GSE320331 肿瘤营养应激导致胰腺癌细胞产生耐药状态
• GSE318648 研究发现，肿瘤相关成纤维细胞中的 FGFBP2 p.T186S 突变通过自分泌和旁分泌机制促进胰腺癌的进展。
• GSE318425 慢性炎症通过ADAM10介导的CX3CL1裂解促进胃癌进展
• GSE316853 N-乙酰半胱氨酸对Nrf2/Keap1通路调控：预防实验性肝细胞癌的关键机制
• GSE315444 鹅胸腺单细胞分析揭示T细胞分化的发育程序和调控逻辑
• GSE285080 HDAC5 缺失促进 FOXA1 过度乙酰化并增强胰腺癌中 HIF1α 转录激活 [ATAC-Seq]
• GSE316495 p300/CREBBP催化活性的抑制驱动急性髓系白血病（AML）中依赖于上下文的转录激活。[ChIP-Seq 2]
• GSE304612 p300/CREBBP催化活性的抑制驱动急性髓系白血病（AML）中依赖于上下文的转录激活。[ChIP-seq]
• GSE304493 p300/CREBBP催化活性的抑制驱动急性髓系白血病（AML）中依赖于特定环境的转录激活。[RNA-seq]
• GSE303021 Hdac11通过抑制Parkin依赖性线粒体自噬，促进巨噬细胞M2型极化和肌成纤维细胞分化，从而促进特发性肺纤维化。
• GSE301454 赖诺普利激活BI1重编程脂质代谢并恢复自噬：探索ALS的新治疗策略
• GSE279644 BCR::ABL1 诱导的增强子重编程揭示 Ph+B-ALL 细胞对靶向增强子的药物的超敏性 [ChIP-Seq]
• GSE279594 BCR::ABL1 诱导的增强子重编程揭示 Ph+B-ALL 细胞对增强子靶向药物的超敏反应 [RNA-Seq]
• GSE230361 用土拉霉素进行预防性治疗的牛的全血 RNA 测序
• GSE318685 IL6 缺失对 Arid1a/Pik3ca 共突变小鼠卵巢肿瘤细胞系基因表达的影响
• GSE303383 高脂饮食诱导的代谢综合征由 JNK7b 同工型促进
• GSE302874 高脂饮食诱发的代谢综合征是由 JNK7b 同工型促进的。
• GSE297857 高脂饮食诱导的代谢综合征由 JNK7b 同工型促进
• GSE243452 Effete 和 Cullin 4 影响吉普赛染色质绝缘子的核组织 [ChIP-Seq]
• GSE243451 Effete 和 Cullin 4 影响吉普赛染色质绝缘子的核组织 [RNA-Seq]
• GSE317990 翻译因子 eIF4G2 通过选择性地激活 IL-7 受体反应来指导 CD8⁺ T 细胞谱系分化
• GSE281332 高脂饮食诱导的代谢综合征由 JNK7b 同工型促进 [inguinalfat_J1J2Liv_RNAseq1]
• GSE278155 高脂饮食诱导的代谢综合征由 JNK7b 同工型促进 [Liver_RNAseq]
• GSE277336 高脂饮食诱导的代谢综合征由 JNK7b 同工型促进
• GSE320297 莱茵衣藻 CreTPT10 突变体在向延长黑暗过渡期间的转录组分析
• GSE320268 KRAS G12C 突变患者基线组织样本的表达分析以及 KRAS G12C 抑制剂治疗期间的纵向血液监测
• GSE320266 KRAS G12C 突变患者接受 KRAS G12C 抑制剂治疗期间血浆样本的表达分析
• GSE317876 青蒿素 (ATT) 的多阶段转录组资源，用于增强肝脏类器官功能和治疗代谢性肝病。
• GSE314202 菱形蛋白酶RHBDL4的缺失会延缓乳腺癌小鼠模型中肿瘤的发生
• GSE313460 植物半乳糖脂对耐药性结直肠癌的影响
• GSE312390 C端闭合蛋白肽通过修复屏障抑制气道炎症
• GSE307350 SKI 对远端抑制元件上胚胎珠蛋白基因的转录抑制 [RNA-seq]
• GSE307347 SKI 对远端抑制元件上胚胎珠蛋白基因的转录抑制 [ChIP-seq]
• GSE302600 RNA结合蛋白Zfp697调控肝脏炎症反应
• GSE290016：恩扎卢胺敏感和耐药的CWR-R1、C4-2B和VCaP细胞的转录组分析
• GSE289910 转录组分析AHR敲低对恩扎卢胺耐药的CWR-R1和C4-2B细胞的影响
• GSE289313 AHR在介导前列腺癌对恩扎卢胺的不同反应中发挥重要作用
• GSE288895 新一代测序技术促进了HAECWT和HAECSAHH-KO的定量分析
• GSE274244 Arx 在发育中的中间神经元中的作用 [scRNA-seq]
• GSE274243 Arx 在发育中的中间神经元中的作用 [ChIP-seq]
• GSE263573 HDAC5 缺失促进 FOXA1 过度乙酰化并增强胰腺癌中 HIF1α 的转录激活
• GSE260513 探索双相情感障碍中PDE5A的上调：来自人类基底神经节单核RNA测序的启示
• GSE226102 基于UPRmt途径的SHP对薄壳性状的调控
• GSE225960 线粒体应激诱导的系统性获得性适应（RNA-Seq）