详细内容（前10条）

1. ⭐ GSE319824 生酮饮食靶向调节全身和肿瘤代谢平衡可增强FLT3-ITD急性髓系白血病的治疗效果

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、leukemia、metabolic
• 📝 描述：Contributors : Jean-Emmanuel Sarry ; Fanny Granat ; Léa Goupille ; Ambrine Sahal ; Tony KaomaSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensFMS-like tyrosine kinase 3 (FLT3) mutations in acute myeloid leukemia (AML) are associated with adverse prognosis. FLT3 inhibitors (FLT3i) improve therapeutic response, however diverse resistance mechanisms such as adaptations in lipid metabolism have been identified. We hypothesized that a lipid-rich ketogenic diet (KD) might alter both host and tumoral lipid metabolism, enhancing responses to FLT3i. In FLT3-mutated AML mouse models, three weeks of lard- or plant-based KD improved efficacy of FLT3i by two-fold reduction of engraftment and tumor burden. KD increased ketone bodies and lipid accumulation in plasma, liver and AML cells, and also induced a PUFA:MUFA imbalance. KD impacted pentoses, hexoses and amino acid metabolism, enhancing sugar phosphates and vitamins in host. Mechanistically, KD rewired anabolism towards fatty acid oxidation and glycine-utilizing pathways, modulated the expression of FLT3 signaling pathways and lipid biosynthesis, and promoted tumor cell differentiation. In conclusion, this study shows that KD reduces FLT3i-resistance, offering a promising therapeutic solution.
• 🔗 查看原文

2. ⭐ GSE311373 FGFR抑制剂克服致癌性PIK3CA驱动的浆液性子宫内膜癌的治疗耐药性和免疫逃逸

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune、regex:onco(logy|logist|gene|genic)、resistance
• 📝 描述：Contributor : Xin ChengSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Mus musculusWe developed the first clinically relevant, immunocompetent SEC mouse model incorporating PIK3CA mutation, TP53 loss, and MYC overexpression. Through comprehensive analysis integrating mouse models, human cell lines, xenografts, and clinical samples, we investigated mechanisms of PIK3CA-targeted therapy resistance. Single-cell transcriptional profiling identified FGFR1/2 association with intrinsic resistance and FGFR3 with acquired resistance. Dual inhibition of FGFR and PI3Ka achieved enhanced tumor suppression. Additionally, we discovered that FGFR signaling promotes immune evasion by downregulating MHC-I/HLA-mediated antigen processing and presentation. Importantly, FGFR inhibition not only reversed immune suppression by restoring antigen presentation but also demonstrated a synergistic effect with anti-PD-1 therapy, enhancing immunotherapy response and anti-tumor immune memory. Our findings reveal FGFR’s dual role in therapy resistance and immune evasion, supporting FGFR inhibition as a promising strategy to enhance treatment outcome in SEC patients.
• 🔗 查看原文

3. ⭐ GSE301939 组蛋白甲基转移酶 DOT1L 影响树突状细胞亚群的发育 [ChIP-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：dendritic cell、ChIP-seq、histone
• 📝 描述：Contributors : Willem-Jan de Leeuw ; Anne Mensink ; Rianne G Bouma ; Fred van Leeuwen ; Joke M den HaanSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusDendritic cells (DCs) are important orchestrators of immune responses and can be divided into two conventional DC subsets, cDC1s and cDC2s, and a plasmacytoid DC (pDC) subset, which are involved in the activation of T cells and production of type I interferons (IFNs), respectively. The development of the DC subsets occurs in the bone marrow (BM) under control of different transcription factors and epigenetic modifiers. The histone methyltransferase DOT1L, known as a druggable target in cancer, is emerging as a key epigenetic regulator of differentiation in lymphocytes. DOT1L writes methylation of lysine 79 of histone H3 in gene bodies of actively transcribed genes. Deletion or inhibition of DOT1L affects the differentiation trajectory of innate and adaptive immune cells, leading to altered cell states. Recent studies suggest that DOT1L also plays a role in DC function. Here, we investigated the role of DOT1L in the development of DCs in in vitro BM cultures and in vivo using a tamoxifen-inducible mouse model. H3K79me2 ChIPseq data of sorted DC subsets from the BM revealed distinct H3K79me2 peaks for all three subsets, which suggested differential regulation of the subsets by DOT1L. A comparison of the H3K79me2 ChIPseq data to bulk RNAseq of sorted DC subsets from the BM revealed a stronger correlation between H3K79me2 and global transcription in pDCs and cDC2s compared to cDC1s. In line with this, we observed that Dot1l deletion led to a decrease in pDCs and CpG A-stimulated IFNα production and an increase in cDC2s in in vitro BM cultures, while cDC1s were unchanged. In vivo deletion of Dot1l led to a decrease in common myeloid progenitors (CMPs), monocyte DC progenitors (MDPs), and common DC progenitors (CDPs) in the BM, while common lymphoid progenitor (CLP) and cDC2 numbers were increased. Inhibition of DOT1L resulted in a similar phenotype, which linked the observed effects to the methyltransferase activity of DOT1L. Interestingly, all Dot1l-KO DC subsets exhibited an enrichment of pathways related to antigen presentation and the immune response and MHCII expression was upregulated in Dot1l-KO pDCs and cDC2s in vivo. To conclude, our data indicate that DOT1L function differentially affects the development of DCs with predominant effects in pDCs and cDC…
• 🔗 查看原文

4. ⭐ GSE301937 组蛋白甲基转移酶 DOT1L 影响树突状细胞亚群的发育 [RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：dendritic cell、RNA-seq、histone
• 📝 描述：Contributors : Willem-Jan de Leeuw ; Anne Mensink ; Rianne G Bouma ; Fred van Leeuwen ; Joke M den HaanSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusDendritic cells (DCs) are important orchestrators of immune responses and can be divided into two conventional DC subsets, cDC1s and cDC2s, and a plasmacytoid DC (pDC) subset, which are involved in the activation of T cells and production of type I interferons (IFNs), respectively. The development of the DC subsets occurs in the bone marrow (BM) under control of different transcription factors and epigenetic modifiers. The histone methyltransferase DOT1L, known as a druggable target in cancer, is emerging as a key epigenetic regulator of differentiation in lymphocytes. DOT1L writes methylation of lysine 79 of histone H3 in gene bodies of actively transcribed genes. Deletion or inhibition of DOT1L affects the differentiation trajectory of innate and adaptive immune cells, leading to altered cell states. Recent studies suggest that DOT1L also plays a role in DC function. Here, we investigated the role of DOT1L in the development of DCs in in vitro BM cultures and in vivo using a tamoxifen-inducible mouse model. H3K79me2 ChIPseq data of sorted DC subsets from the BM revealed distinct H3K79me2 peaks for all three subsets, which suggested differential regulation of the subsets by DOT1L. A comparison of the H3K79me2 ChIPseq data to bulk RNAseq of sorted DC subsets from the BM revealed a stronger correlation between H3K79me2 and global transcription in pDCs and cDC2s compared to cDC1s. In line with this, we observed that Dot1l deletion led to a decrease in pDCs and CpG A-stimulated IFNα production and an increase in cDC2s in in vitro BM cultures, while cDC1s were unchanged. In vivo deletion of Dot1l led to a decrease in common myeloid progenitors (CMPs), monocyte DC progenitors (MDPs), and common DC progenitors (CDPs) in the BM, while common lymphoid progenitor (CLP) and cDC2 numbers were increased. Inhibition of DOT1L resulted in a similar phenotype, which linked the observed effects to the methyltransferase activity of DOT1L. Interestingly, all Dot1l-KO DC subsets exhibited an enrichment of pathways related to antigen presentation and the immune response and MHCII expression was upregulated in Dot1l-KO pDCs and cDC2s in vivo. To conclude, our data indicate that DOT1L function differentially affects the development of DCs with predominant effects in pDCs and cDC2s.
• 🔗 查看原文

5. ⭐ GSE292814 FGFR抑制剂克服致癌性PIK3CA驱动的浆液性子宫内膜癌的治疗耐药性和免疫逃逸

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune、regex:onco(logy|logist|gene|genic)、resistance
• 📝 描述：Contributor : Xin ChengSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusWe developed the first clinically relevant, immunocompetent SEC mouse model incorporating PIK3CA mutation, TP53 loss, and MYC overexpression. Through comprehensive analysis integrating mouse models, human cell lines, xenografts, and clinical samples, we investigated mechanisms of PIK3CA-targeted therapy resistance. Single-cell transcriptional profiling identified FGFR1/2 association with intrinsic resistance and FGFR3 with acquired resistance. Dual inhibition of FGFR and PI3Ka achieved enhanced tumor suppression. Additionally, we discovered that FGFR signaling promotes immune evasion by downregulating MHC-I/HLA-mediated antigen processing and presentation. Importantly, FGFR inhibition not only reversed immune suppression by restoring antigen presentation but also demonstrated a synergistic effect with anti-PD-1 therapy, enhancing immunotherapy response and anti-tumor immune memory. Our findings reveal FGFR’s dual role in therapy resistance and immune evasion, supporting FGFR inhibition as a promising strategy to enhance treatment outcome in SEC patients.
• 🔗 查看原文

6. ⭐ GSE320216 乳腺癌进展过程中基因组重组及其功能影响 [RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、RNA-seq、genome
• 📝 描述：Contributors : Kathleen S Reed ; Tom Misteli ; Andrew Fritz ; Haley Greenyer ; Seth Frietze ; Janet Stein ; Gary SteinSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensTo explore how chromatin structure and epigenetic parameters of genome architecture changes during cancer progression at a fine scale and genome-wide, we generated high-resolution Micro-C contact maps in non-malignant, pre-cancerous, and metastatic MCF10 breast cancer epithelial cells. We profiled progression-associated reorganization of chromatin compartments, topologically associated domains (TADs), and chromatin loops, and also identified invariable chromatin features. We find large-scale compartmental shifts occur predominantly in early stages of cancer development, with more fine-scale structural changes in TADs and looping accumulating during the later transition to metastasis. We related these structural features to changes in gene expression, histone marks, and potential enhancers and found a large portion of differentially expressed genes physically connected to distal regulatory elements. While changes in chromatin loops were relatively rare during progression, differential loops were enriched for progression-associated genes, including those involved in proliferation, angiogenesis, and differentiation. Changes in either enhancer-promoter contacts or distal enhancer activity were accompanied by differential gene regulation, suggesting that changes in chromatin contacts are not necessary but can be sufficient for gene regulation. Together, our results demonstrate a functionally relevant connection between gene regulation and genome remodeling at many key genes during cancer progression.
• 🔗 查看原文

7. ⭐ GSE320215 乳腺癌进展过程中基因组重组及其功能影响 [ATAC-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、ATAC-seq、genome
• 📝 描述：Contributors : Kathleen S Reed ; Tom Misteli ; Andrew Fritz ; Haley Greenyer ; Seth Frietze ; Janet Stein ; Gary SteinSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensTo explore how chromatin structure and epigenetic parameters of genome architecture changes during cancer progression at a fine scale and genome-wide, we generated high-resolution Micro-C contact maps in non-malignant, pre-cancerous, and metastatic MCF10 breast cancer epithelial cells. We profiled progression-associated reorganization of chromatin compartments, topologically associated domains (TADs), and chromatin loops, and also identified invariable chromatin features. We find large-scale compartmental shifts occur predominantly in early stages of cancer development, with more fine-scale structural changes in TADs and looping accumulating during the later transition to metastasis. We related these structural features to changes in gene expression, histone marks, and potential enhancers and found a large portion of differentially expressed genes physically connected to distal regulatory elements. While changes in chromatin loops were relatively rare during progression, differential loops were enriched for progression-associated genes, including those involved in proliferation, angiogenesis, and differentiation. Changes in either enhancer-promoter contacts or distal enhancer activity were accompanied by differential gene regulation, suggesting that changes in chromatin contacts are not necessary but can be sufficient for gene regulation. Together, our results demonstrate a functionally relevant connection between gene regulation and genome remodeling at many key genes during cancer progression.
• 🔗 查看原文

8. GSE315728 MS 患者肠道中回肠上皮和免疫细胞谱的改变。

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune、regex:intestin(e|al)
• 📝 描述：Contributors : Shohei Suzuki ; Kentaro Miyamoto ; Jonathan Moody ; Tomohisa SujinoSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensThe intestinal epithelium plays a critical role in immune–microbiota interactions, yet its contribution to systemic autoimmunity remains unclear. Here, we identify intestinal epithelial cells (IECs) as key initiators of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). In MS patients, IECs upregulate antigen presentation–related genes and associate with increased intestinal Th17 cell accumulation.
• 🔗 查看原文

9. GSE320388 氮代谢谱分析揭示细胞状态特异性嘧啶合成途径选择

• ✍️ 作者：未知作者
• 🏷️ 关键词：metabolism、pathway
• 📝 描述：Contributors : Milan R Savani ; Bingbing Li ; Tracey Shipman ; Samuel K McBrayerSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensStable isotope tracing assays track few metabolites, yet cells use many nutrients to sustain nitrogen metabolism. Here, we create a platform for tracing 30 nitrogen isotope-labeled metabolites in parallel to enable a system-level understanding of cellular nitrogen metabolism. This platform reveals that while primitive cells engage both de novo and salvage pyrimidine synthesis pathways, differentiated cells nearly exclusively salvage uridine. This link between cell state and pyrimidine synthesis pathway preference persists in murine and human tissues. Mechanistically, we find that S1900 phosphorylation of CAD, the first enzyme of the de novo pathway, is induced by uridine deprivation in differentiated cells and constitutively enriched in primitive cells. Mimicking CAD S1900 phosphorylation in differentiated cells constitutively activates de novo pyrimidine synthesis, while blocking this modification impairs the cellular response to uridine starvation. Collectively, we establish a method for nitrogen metabolism profiling and define a mechanism of cell state-specific pyrimidine synthesis pathway choice.
• 🔗 查看原文

10. GSE308878 纤毛细胞通过STING介导的肿瘤抑制的免疫非依赖性机制阻止肿瘤发生

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、immune
• 📝 描述：Contributors : Jose A Colina ; Rong Wu ; Brian Magnuson ; Kathleen R Cho ; Analisa DiFeoSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusMitigating DNA damage in the fallopian tube epithelium (FTE) is essential for preventing tubo-ovarian high-grade serous carcinoma (HGSC). Here we demonstrate that Stimulator of Interferon Genes (STING) is abundantly expressed in the ciliated cells of the FTE and functions as a critical immune-independent tumor suppressor. Using patient samples, mouse models, and organoid systems, we demonstrate that ciliated cells mount a dual protective response to ovulation-associated genotoxic stress: intrinsic STING-driven apoptosis and extrinsic clearance of neighboring damaged secretory cells via TNFα secretion. This surveillance mechanism markedly limits DNA damage accumulation within the epithelial microenvironment. Crucially, while these mechanisms are vital for maintaining homeostasis and reducing genomic instability, they fail to impact p53-deficient precursor lesions as both intrinsic and extrinsic pro-apoptotic processes rely on functional p53 signaling. These findings redefine ciliated cells as key guardians of genome integrity rather than passive bystanders and implicate early loss of STING-high ciliated cells as a pivotal event in HGSC initiation with potential relevance for prevention and therapeutic intervention.
• 🔗 查看原文

💡 该来源还有 42 条内容，详见 文末

详细内容（全部1条）

1. 阿尔茨海默病可能始于脑血流量的悄然下降。

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer
• 📝 描述：Subtle changes in brain blood flow and oxygen use are closely linked to hallmark signs of Alzheimer’s, including amyloid plaques and memory-related brain shrinkage. Simple, noninvasive scans may one day help spot risk earlier—by looking at the brain’s vascular health, not just its plaques.
• 🔗 查看原文

• 对从小鼠乳腺肿瘤中分离的 CD45 阳性细胞进行了 GSE300991 单细胞 RNA 测序分析。
• GSE281293 KSHV裂解性再激活后的全基因组转录组分析
• GSE319658 选择性靶向组蛋白样沉默子 Sfx 至 R6K 接合转移操纵子 [ChIP-Seq]
• GSE319657 组蛋白样沉默子 Sfx 选择性靶向 R6K 接合转移操纵子 [RNA-Seq]
• GSE320319 基因组重组及其在乳腺癌进展过程中的功能影响
• GSE302079 膀胱癌基因工程小鼠模型衍生肿瘤细胞系的表征
• GSE287674 MafB 是跨组织和物种的巨噬细胞发育和身份的保守转录调节因子 [scRNA-Seq]
• GSE286897 MafB 是跨组织和物种的巨噬细胞发育和身份的保守转录调节因子 [RNA-seq]
• GSE320312 抗TIM3-IFN融合蛋白通过激活肿瘤内树突状细胞，使肿瘤浸润的耗竭TIM3+CD8+T细胞恢复活力
• GSE320308 PD0325901 Alleviates Thrombin-Inhibited Osteogenic Differentiation Through an IL-1β-Activated Feedback Loop between MEK-Erk1/2 and NF-κB Signal Pathways: Insights from Bioinformatics and Experimental Verification
• GSE307339 炎症增强成年APP小胶质细胞在微流控神经元-小胶质细胞共培养模型中的突触特异性吞噬作用
• GSE305554 m6A 表观转录组调控视网膜神经节细胞的轴突发生和重编程 [RNA-seq]
• GSE296812：组蛋白修饰时钟在跨物种生物年龄预测中的稳健应用及衰老调控机制的阐明
• GSE234721 果蝇 piRNA 簇异染色质在急性热休克后的快速解体和 Piwi 非依赖性重组 [RNA-seq]
• GSE315447 22q11.2微缺失位点编码的单倍体不足线粒体基因之间的抑制性遗传相互作用决定了大脑和心脏表型
• GSE307353 Siglec-F 可保护小鼠免受弹性蛋白酶诱导的肺部炎症和肺气肿
• GSE304577 慢性可卡因使用障碍中口腔到血液微生物DNA易位的特征分析
• GSE292232 小鼠后肢骨骼肌在胚胎期和成年期慢肌纤维含量差异的基因组特征[RNA-Seq]
• GSE292230 小鼠后肢骨骼肌在胚胎期和成年期慢肌纤维含量差异的基因组特征 [ATAC-Seq]
• GSE281295 KSHV裂解性再激活过程中细胞miRNA转录组的特征分析
• GSE315102 白细胞介素-2-TGF-β 替代激动剂可轻松诱导免疫耐受
• GSE314399 人类 Flower 同工型 hFWE4 促进皮肤鳞状细胞癌的角化
• GSE313932 FOXO1 整合动脉粥样硬化中的内皮血流动力学、炎症和代谢通路 [LSS]
• GSE313931 FOXO1 整合动脉粥样硬化中的内皮血流动力学、炎症和代谢通路 [OSS]
• GSE285051 人类干细胞衍生睾丸样类器官中多种睾丸细胞谱系的出现 [scRNA-Seq]
• GSE285050 人类干细胞衍生睾丸样类器官中多种睾丸细胞谱系的出现 [RNA-Seq]
• GSE268687 nBAF复合物亚基CREST/SS18L1通过酪氨酸397和组蛋白乙酰转移酶CBP调节海马记忆过程
• GSE243065 基因组编辑中最大限度减少大范围染色质扰动可保护干细胞特性
• GSE320155 人类肝内 CD4⁺ T 细胞的单细胞 RNA 测序结果揭示了健康肝脏和肝细胞癌 (HCC) 肝脏样本中独特的 Treg 转录特征和两种稳态组织适应程序。
• GSE320120 硫代黄素通过重塑酵母转录和代谢延长复制寿命
• GSE303683 RNA-seq 数据来自 GBM 患者和配对类器官
• GSE303409 鉴定肺癌放射抗性基因 [CRISPR 筛选]
• GSE303209 肠隐窝是戊型肝炎病毒感染的潜在储存库
• GSE299009 低强度超声 (LIUS) 诱导的非小细胞肺癌 (NSCLC) 细胞系转录组改变。
• GSE295920 膀胱癌的基因工程小鼠模型和同基因移植模型
• GSE291409 BALF 基因表达谱分析揭示了 COVID-19 后持续性 ILD 中先天免疫激活的偏倚
• GSE290421 二十二碳六烯酸通过其氧脂质保护肺部免受臭氧诱导的炎症。
• GSE290387 对 1-5 岁幼儿鼻腔刮匙或拭子样本进行 RNA 测序
• GSE287476 MafB 是跨组织和物种的巨噬细胞发育和身份的保守转录调节因子 [CUT&RUN 2]
• GSE287347 MafB 是巨噬细胞发育和特性在不同组织和物种中保守的转录调控因子。
• GSE287346 MafB 是跨组织和物种的巨噬细胞发育和身份的保守转录调节因子 [CUT&Run]
• GSE272963 恶性疟原​​虫临床样本中线粒体天然反义转录本的差异表达在多种疾病表型中的研究