详细内容（前10条）

1. ⭐ GSE314707 利用膜近端 AXL 抗体重编程肿瘤微环境以克服免疫检查点阻断耐药性

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、immune、tumor microenvironment、antibody、resistance
• 📝 描述：Contributors : Zuming Yang ; Shuai CaoSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusImmune-cold tumors failed to respond to immunotherapy due to insufficient lymphocytes infiltration within tumor tissue. How to increase the objective response rate is an urgent challenge. Here, we report the development of a monoclonal antibody (6C5) that specifically targets the membrane-proximal epitope of receptor tyrosine kinase AXL, which modulates the anti-tumor immunity. Unlike traditional membrane-distal AXL antibodies, 6C5 significantly enhanced innate immune sensing by promoting macrophage-mediated antigen uptake and type I interferon production via the MyD88 pathway. This reshaped the tumor microenvironment , further boosting CD8+ T cell infiltration and effector function. However, AXL antibody treatment concurrently induced a suppressive subset of PD-1hiFoxp3-CD4+ T cell, attenuating antitumor responses. The combination of AXL Ab with dual immune checkpoint blockade (anti-PD-1 plus anti-CTLA-4) or PD-1-targeted IL-2 fusion protein therapy mitigated this immunosuppression, achieving potent tumor regression and durable immune memory. Our findings demonstrate that membrane-proximal AXL targeting antibody effectively converts immune-cold tumor microenvironment, overcoming resistance to both conventional and next-generation immune checkpoint inhibitors.
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2. ⭐ GSE285791 人参皂苷Rb1和黄连素通过GDF15/HAMP信号通路在肝小叶中对2型糖尿病发挥协同保护作用：空间转录组学分析的启示

• ✍️ 作者：未知作者
• 🏷️ 关键词：spatial、spatial transcriptomics、transcriptomics、pathway
• 📝 描述：Contributors : Rongfang Guo ; Shuying Zhang ; Anyao Li ; Ping Zhang ; Xin Peng ; Xiaoyan Lu ; Xiaohui FanSeries Type : OtherOrganism : Mus musculusType 2 diabetes mellitus (T2DM) is a significant public health issue with high mortality and morbidity. Ginsenoside Rb1 and berberine, the main bioactive compounds of Panax ginseng and Coptis chinensis, respectively, are known for their hypoglycemic effects. Nevertheless, the synergistic effects and underlying mechanism of ginsenoside Rb1 and berberine on T2DM remain unclear. In this study, we utilized a leptin receptor- deficient (db/db) mouse model to investigate the protective effects of their combination treatment. Our findings demonstrated that the combined use of ginsenoside Rb1 and berberine at a 1:4 ratio had more pronounced effects than the first-line anti-diabetic drug metformin on reducing the weight ratio of white adipose tissue, ameliorating insulin resistance, and improving glucose and lipid metabolism. Using spatial transcriptomics, we revealed that metformin treatment improved gluconeogenesis and lipogenesis only in the periportal zone, while the combination treatment induced improvements throughout the liver lobule, with distinct key targets across different zones, thus underscoring a more comprehensive and nuanced modulation of hepatic metabolism. This may be the key reason why this combination therapy demonstrated superior protective effects against T2DM. Additionally, the reversed expression of the key callback gene Hamp and its regulator Gdf15 following the combination therapy across all zones, along with validation experiments, further suggested that the GDF15/HAMP signaling pathway might be a key mechanism underlying the beneficial effects of ginsenoside Rb1 and berberine against T2DM. This study also indicates a path toward innovative drug cocktails for treating T2DM, offering a holistic approach to regulate the entire liver lobule metabolism.
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3. ⭐ GSE314457 基质细胞对脂肪酸的代谢适应驱动口腔鳞状细胞癌的转移 [RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：carcinoma、metabolic、RNA-seq
• 📝 描述：Contributors : Yiling Duan ; Yitong Li ; Yufei Wu ; Rui Li ; Xiao Yang ; Hui Zhao ; Zhengjun ShangSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensMetabolic adaptation enables cancer cell survival under nutrient stress, but how stromal cells in tumor microenvironment (TME) withstand similar metabolic change remains elusive. Here, we report that fatty acids (FAs), a nutrient with dual roles in energy provision and lipotoxicity, orchestrate a pro-metastatic adaptation program in cancer-associated fibroblasts (CAFs). In patients with oral squamous cell carcinoma (OSCC), the FA transporter CD36 was upregulated not only in cancer cells but also in myofibroblastic CAFs (myoCAFs), where it correlated with more advanced metastasis stage. Among 5 kinds of FAs enriched in OSCC tissues, palmitic acid (PA) potently activated myoCAFs phenotypes across 2D, 3D, and organoid co-culture models. In vivo, PA promoted lymph node metastasis in orthotopic tumors comprising OSCC cells and CAFs, an effect abolished by CD36 knockdown in CAFs. Mechanistically, PA engaged chromatin occupancy of H3K27ac at multiple genes including IRE1 and TMBIM6, two stress-adaptive regulators. Transcription of IRE1 and TMBIM6 in CAFs was regulated by CCAAT/enhancer-binding protein γ (CEBPG) through an enhancer-dependent manner. Disruption of the CEBPG–IRE1/TMBIM6 axis attenuated myoCAFs properties and abrogated PA-driven metastasis. Our results unveil a stromal metabolic checkpoint and establish CEBPG-enhanced stress resilience as a therapeutic target to curtail metastasis.
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4. GSE252113 通过单细胞多组学分析剖析肾上腺皮质癌的肿瘤内和肿瘤间异质性

• ✍️ 作者：未知作者
• 🏷️ 关键词：carcinoma、single-cell
• 📝 描述：Series Type : OtherOrganism : Homo sapiensThis SuperSeries is composed of the SubSeries listed below.
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5. GSE252112 通过单细胞多组学分析剖析肾上腺皮质癌的肿瘤内和肿瘤间异质性[II]

• ✍️ 作者：未知作者
• 🏷️ 关键词：carcinoma、single-cell
• 📝 描述：Contributors : Xiangyu Pan ; Shengzhuo Liu ; Yu Liu ; Chong ChenSeries Type : OtherOrganism : Homo sapiensAdrenocortical carcinoma (ACC) is a rare but aggressive malignancy originating in the adrenal cortex, characterized by significant intra- and intertumoral heterogeneity. In this study, we employed a combination of whole-genome sequencing, single-cell RNA sequencing, T cell receptor sequencing, spatial transcriptome sequencing, and multiple fluorescent staining to construct a comprehensive multi-omics landscape of ACC. Our findings demonstrated that, although all tumor cells exhibited a “confused cell identity” feature, distinct subpopulations were present in each ACC patient. Among these, the LDLR+ and MKI67+ subpopulations expressed elevated levels of C1A signature genes and established robust communication with endothelial cells through NECTIN-PVR and NOTCH2-JAG pairs, both significantly associated with poor prognosis. Interestingly, the PCDH15+ subpopulations displayed moderate levels of both C1A signature genes and extracellular matrix related genes. On the other hand, the HLA-B+ and subpopulation exhibited the highest levels of antigen-processing related genes, a characteristic not previously reported. The amalgamation of these distinct subpopulations facilitated the stratification of ACC patients into subtypes with varying prognoses. Patients (Group II) dominated by LDLR+ and MKI67+ subpopulations exhibited the worst prognosis, while those (Group III) with a higher proportion of PCDH15+ subpopulation demonstrated the most favorable outcomes. Significantly, patients (Group I) with a higher prevalence of the HLA-B+ subpopulation also showed notably increased LAG3+ memory CD8 T cells, indicating their potential suitability for immunotherapy. Despite responding averagely to conventional treatment, this subgroup was predicted to be responsive to immunotherapy. Notably, one patient from Group I exhibited a positive response to camrelizumab treatment after relapse with mitotane, leading to a successful outcome, while two patients from Group II did not respond favorably. Our study offers insights into the single-cell level heterogeneity of ACC and provides valuable implications for precision treatments for this disease.
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6. GSE252108 通过单细胞多组学分析剖析肾上腺皮质癌的肿瘤内和肿瘤间异质性[I]

• ✍️ 作者：未知作者
• 🏷️ 关键词：carcinoma、single-cell
• 📝 描述：Contributors : Xiangyu Pan ; Shengzhuo Liu ; Yu Liu ; Chong ChenSeries Type : OtherOrganism : Homo sapiensAdrenocortical carcinoma (ACC) is a rare but aggressive malignancy originating in the adrenal cortex, characterized by significant intra- and intertumoral heterogeneity. In this study, we employed a combination of whole-genome sequencing, single-cell RNA sequencing, T cell receptor sequencing, spatial transcriptome sequencing, and multiple fluorescent staining to construct a comprehensive multi-omics landscape of ACC. Our findings demonstrated that, although all tumor cells exhibited a “confused cell identity” feature, distinct subpopulations were present in each ACC patient. Among these, the LDLR+ and MKI67+ subpopulations expressed elevated levels of C1A signature genes and established robust communication with endothelial cells through NECTIN-PVR and NOTCH2-JAG pairs, both significantly associated with poor prognosis. Interestingly, the PCDH15+ subpopulations displayed moderate levels of both C1A signature genes and extracellular matrix related genes. On the other hand, the HLA-B+ and subpopulation exhibited the highest levels of antigen-processing related genes, a characteristic not previously reported. The amalgamation of these distinct subpopulations facilitated the stratification of ACC patients into subtypes with varying prognoses. Patients (Group II) dominated by LDLR+ and MKI67+ subpopulations exhibited the worst prognosis, while those (Group III) with a higher proportion of PCDH15+ subpopulation demonstrated the most favorable outcomes. Significantly, patients (Group I) with a higher prevalence of the HLA-B+ subpopulation also showed notably increased LAG3+ memory CD8 T cells, indicating their potential suitability for immunotherapy. Despite responding averagely to conventional treatment, this subgroup was predicted to be responsive to immunotherapy. Notably, one patient from Group I exhibited a positive response to camrelizumab treatment after relapse with mitotane, leading to a successful outcome, while two patients from Group II did not respond favorably. Our study offers insights into the single-cell level heterogeneity of ACC and provides valuable implications for precision treatments for this disease.
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7. GSE285991 化疗通过促进肝转移瘤中LEPR+库普弗细胞分化来触发免疫逃逸

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune
• 📝 描述：Contributors : Xuege Wang ; Qiang PanSeries Type : Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencing ; OtherOrganism : Homo sapiens ; Mus musculusThis SuperSeries is composed of the SubSeries listed below.
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8. GSE314794 长春新碱通过下调Tssk4和Ccdc159诱导B-ALL PDX小鼠模型精子发生障碍：RNA-seq转录组分析

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq
• 📝 描述：Contributors : Chaoming Zhou ; Meng Fu ; Suyun Chen ; Shengqi Zheng ; Xu CuiSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThis dataset contains RNA sequencing (RNA-seq) data generated from testicular tissues of a B-cell acute lymphoblastic leukemia (B-ALL) patient-derived xenograft (PDX) mouse model treated with vincristine (VCR). The study aimed to elucidate the molecular mechanisms underlying VCR-induced reproductive toxicity. Samples were collected from multiple experimental groups, including normal controls (NC), leukemia-bearing controls (ALL), and VCR-treated groups with varying leukemia infiltration levels. Transcriptomic analysis revealed widespread gene expression perturbations following VCR exposure, with significant downregulation of genes crucial for spermatogenesis and sperm flagellar assembly. This data provides a comprehensive resource for understanding the genetic pathways affected by VCR in the testicular microenvironment.
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9. GSE314727 VGSC 突变和 P450 过表达与枸杞田棉蚜（Aphis gossypii Glover）的 β-氯氰菊酯抗性相关

• ✍️ 作者：未知作者
• 🏷️ 关键词：resistance
• 📝 描述：Contributors : Fang Wang ; Shujing Zhang ; Yunfei ZhangSeries Type : Expression profiling by high throughput sequencingOrganism : Aphis gossypiiIdentification and characterization of genes and target-site mutations associated with beta-cypermethrin resistance in Aphis gossypii Glover collected from a Chinese wolfberry (Lycium barbarum L.) field. we collected a beta-cypermethrin resistant A. gossypii strain (HSP) from a Chinese wolf-berry orchard in a major growing area of Ningxia wolfberry (Wuzhong city). Subsequently, to elucidate the potential roles of P450s, CarEs and GSTs in beta-cypermethrin resistance in the A. gossypii strain, we performed synergistic bioassays, as well as enzyme activity assays, to confirm their effects. Further, we carried out a comparative transcriptome anal-ysis to identified the overexpression of detoxification enzyme genes associated with the beta-cypermethrin resistance. According to the transcriptome variations, we also meas-ured the expression levels of the upregulated P450s genes involved in beta-cypermethrin resistance in the A. gossypii resistant strain, using a quantitative real-time PCR assay. Moreover, the potential mutations in VGSC genes and their frequencies were detected to reveal the VGSC genotype of the resistant strain.
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10. GSE314683 染色质组装因子 1 是粗糙脉孢菌正常基因抑制和兼性异染色质形成所必需的 [ChIP-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：ChIP-seq
• 📝 描述：Contributors : Eduardo V Torres ; Collin D Link ; Rochelle Yap ; Aileen R Ferraro ; Abigail M Deaven ; Jackie F Pelham ; Zachary A LewisSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Neurospora crassaFormation of facultative heterochromatin by Polycomb Repressive Complex 2 (PRC2) is a well conserved epigenetic mechanism that functions to control transcriptional dynamics across eukaryotes. PRC2 catalyzes histone H3 lysine 27 tri-methylation (H3K27me3), a histone post-translational modification that helps maintain stable gene repression. Gene repression by PRC2 is important for organismal development and defects in PRC2 function are associated with human ailments, such as Weaver syndrome and various cancers. In this study, we reveal the replication-dependent histone chaperone, Chromatin Assembly Factor 1 (CAF-1), is required for normal facultative heterochromatin formation in model fungus N. crassa. CAF-1 deficiency results in widespread misregulation of gene expression, particularly within facultative heterochromatin domains, which is accompanied by a rearrangement of H3K27me3 patterns. Regional losses of H3K27me3 are associated with reduced levels of ASH-1 catalyzed H3K36 methylation, and gains of histone modifications associated with active transcription. Furthermore, analysis of a double mutant deficient for both CAF-1 and PRC2 activity revealed that these complexes play distinct roles in maintaining gene repression and facultative heterochromatin. Collectively, these results shed light on CAF-1’s role in maintaining a repressive chromatin environment.
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💡 该来源还有 7 条内容，详见 文末

• GSE314682 染色质组装因子 1 是粗糙脉孢菌正常基因抑制和兼性异染色质形成所必需的 [RNA-seq]
• GSE313930 小鼠主动脉平滑肌细胞中Ano1缺陷引起的染色质状态变化的全基因组图谱
• GSE294848 翻译保留的第11号内含子序列赋予阿尔茨海默病中Tau蛋白病理特性
• GSE284309 cMaf 支持 Zeb2 在原始造血中的表达（FL 单 RNA-seq）
• GSE283975 cMaf 支持 Zeb2 在原始造血中的表达（TRM RNA-seq）
• GSE254169 高质量的石斛染色体水平参考基因组为苦味素型倍半萜生物碱的生物合成和积累提供了新的见解
• GSE251891 AUF1 通过调控听觉毛细胞中免疫反应基因的转录和选择性剪接来调节衰老