详细内容（前10条）

1. ⭐ GSE313918 肌萎缩侧索硬化症中语言和执行功能衰退的差异性细胞机制 [Visium 空间转录组学]

• ✍️ 作者：未知作者
• 🏷️ 关键词：spatial、Visium、spatial transcriptomics、transcriptomics
• 📝 描述：Contributors : C Jackson ; A Daly ; C Roque ; J Petrescu ; H PhatnaniSeries Type : OtherOrganism : Homo sapiensHalf of all amyotrophic lateral sclerosis (ALS) patients demonstrate a spectrum of cognitive and behavioral changes over the course of the disease, but the mechanisms underlying this heterogeneity remain unclear. We assemble a high-resolution cellular map of prefrontal cortex regions of the ALS brain by integrating spatial and single-nucleus transcriptomic profiles of a cognitively stratified ALS patient cohort that includes non-neuropathological controls. We find cellular programs characteristic of ALS, including a frequent gliotic response. We also find that executive and language cognitive impairments differ from ALS without cognitive impairment, and from each other, in the extent and pattern of neuronal dysregulation and neuron-glial interactions across different brain regions. These findings reveal a relationship between cognitive phenotype and prefrontal cortex dysfunction in ALS.
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2. ⭐ GSE169273 通过单核甲基化测序研究大脑衰老的表观遗传特征 [DHC-18mo-m-002]

• ✍️ 作者：未知作者
• 🏷️ 关键词：aging、sequencing、epigenetic、methylation
• 📝 描述：Contributors : Wei Tian ; Anna Bartlett ; Jordan Altshul ; Rosa Gomez Castanon ; Joseph R Nery ; Jacinta D Lucero ; Julia K Osteen ; Huaming Chen ; M M Behrens ; Joseph R EckerSeries Type : Methylation profiling by high throughput sequencingOrganism : Mus musculusIllustrating aging effects on the epigenomic features of brain is critical to understand brain functional decline and neurodegeneration. Single nucleus methylation sequencing was applied to brain regions of mouse at the age of 2, 9 and 18 months. We use these data to identify the epigenomic changes with aging in mouse brains.
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3. ⭐ GSE299509 表观遗传疗法联合 FACT 和 BET 抑制剂可重塑染色质并破坏弥漫性中线胶质瘤中的致癌转录 [新生 RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：glioma、regex:onco(logy|logist|gene|genic)、RNA-seq、epigenetic
• 📝 描述：Contributors : Holly Holliday ; Chelsea MayohSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAberrant epigenetic regulation is a hallmark of Diffuse Midline Glioma (DMG), an incurable pediatric brain tumor. The H3K27M driver histone mutation leads to transcriptional dysregulation, indicating that targeting the epigenome and transcription may be key therapeutic strategies against this highly aggressive cancer. One such target is the Facilitates Chromatin Transcription (FACT) histone chaperone. We found FACT to be enriched at developmental gene promoters, coinciding with regions of open chromatin and binding motifs of core DMG regulatory transcription factors. Furthermore, FACT interacted and co-localized with the Bromodomain and Extra-Terminal Domain (BET) protein BRD4 at promoters and enhancers, suggesting functional cooperation between FACT and BRD4 in DMG. In vitro, a combinatorial therapeutic approach using the FACT inhibitor CBL0137, coupled with BET inhibition revealed potent and synergistic cytotoxicity across a range of DMG cultures. These results were recapitulated in vivo, significantly extending survival in three independent orthotopic PDX models of DMG. Mechanistically, we show that CBL0137 treatment decreased chromatin accessibility, synergizing with BET inhibition to cause broad transcriptional collapse, silencing several key oncogenes including MYC, PDGFRA, MDM4 and SOX2, as well as causing alterations to the splicing landscape. Notably, this combination also elicited immune-related effects, including activation of the interferon response and antigen presentation mechanisms in DMG cells and induction of an activated state in macrophages and T cells, as demonstrated in an immunocompetent setting with spatial transcriptomics. Altogether, our data highlights the therapeutic promise of simultaneously targeting FACT and BET proteins in DMG, offering a dual tumor-intrinsic and immune-mediated strategy for combating this devastating pediatric brain tumor.
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4. ⭐ GSE272131 表观遗传疗法联合 FACT 和 BET 抑制剂可重塑染色质并破坏弥漫性中线胶质瘤中的致癌转录 [RNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：glioma、regex:onco(logy|logist|gene|genic)、RNA-seq、epigenetic
• 📝 描述：Contributors : Holly Holliday ; Nisitha Jayatilleke ; Chelsea Mayoh ; Xinyi GuoSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAberrant epigenetic regulation is a hallmark of Diffuse Midline Glioma (DMG), an incurable pediatric brain tumor. The H3K27M driver histone mutation leads to transcriptional dysregulation, indicating that targeting the epigenome and transcription may be a key therapeutic strategy against this highly aggressive cancer. One such target is the Facilitates Chromatin Transcription (FACT) histone chaperone. We found FACT to be enriched at developmental gene promoters, coinciding with regions of open chromatin and binding motifs of core DMG regulatory transcription factors. Furthermore, FACT interacted and co-localized with the Bromodomain and Extra-Terminal Domain (BET) protein BRD4 at promoters and enhancers, suggesting functional cooperation between FACT and BRD4 in DMG. In vitro, a combinatorial therapeutic approach using the FACT inhibitor CBL0137, coupled with BET inhibition revealed potent and synergistic cytotoxicity across a range of DMG cultures, with H3K27M-mutant cells demonstrating heightened sensitivity. These results were recapitulated in vivo, significantly extending survival in three independent orthotopic PDX models of DMG. Mechanistically, we show that CBL0137 treatment decreased chromatin accessibility, synergizing with BET inhibition to disrupt transcription, silencing several key oncogenes including MYC, PDGFRA and MDM4, alongside alterations to the splicing landscape. Combined, these data highlight the therapeutic promise of simultaneously targeting FACT and BRD4 in DMG, proposing a novel strategy for combating this devastating pediatric brain tumor.
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5. ⭐ GSE272129 表观遗传疗法联合 FACT 和 BET 抑制剂可重塑染色质并破坏弥漫性中线胶质瘤中的致癌转录 [ATAC-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：glioma、regex:onco(logy|logist|gene|genic)、ATAC-seq、epigenetic
• 📝 描述：Contributors : Holly Holliday ; Nisitha Jayatilleke ; Chelsea Mayoh ; Samuel E RossSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensAberrant epigenetic regulation is a hallmark of Diffuse Midline Glioma (DMG), an incurable pediatric brain tumor. The H3K27M driver histone mutation leads to transcriptional dysregulation, indicating that targeting the epigenome and transcription may be a key therapeutic strategy against this highly aggressive cancer. One such target is the Facilitates Chromatin Transcription (FACT) histone chaperone. We found FACT to be enriched at developmental gene promoters, coinciding with regions of open chromatin and binding motifs of core DMG regulatory transcription factors. Furthermore, FACT interacted and co-localized with the Bromodomain and Extra-Terminal Domain (BET) protein BRD4 at promoters and enhancers, suggesting functional cooperation between FACT and BRD4 in DMG. In vitro, a combinatorial therapeutic approach using the FACT inhibitor CBL0137, coupled with BET inhibition revealed potent and synergistic cytotoxicity across a range of DMG cultures, with H3K27M-mutant cells demonstrating heightened sensitivity. These results were recapitulated in vivo, significantly extending survival in three independent orthotopic PDX models of DMG. Mechanistically, we show that CBL0137 treatment decreased chromatin accessibility, synergizing with BET inhibition to disrupt transcription, silencing several key oncogenes including MYC, PDGFRA and MDM4, alongside alterations to the splicing landscape. Combined, these data highlight the therapeutic promise of simultaneously targeting FACT and BRD4 in DMG, proposing a novel strategy for combating this devastating pediatric brain tumor.
• 🔗 查看原文

6. ⭐ GSE169345 通过单核甲基化测序研究大脑衰老的表观遗传特征 [DHC-18mo-m-003]

• ✍️ 作者：未知作者
• 🏷️ 关键词：aging、sequencing、epigenetic、methylation
• 📝 描述：Contributors : Wei Tian ; Anna Bartlett ; Jordan Altshul ; Rosa Gomez Castanon ; Joseph R Nery ; Jacinta D Lucero ; Julia K Osteen ; Huaming Chen ; M M Behrens ; Joseph R EckerSeries Type : Methylation profiling by high throughput sequencingOrganism : Mus musculusIllustrating aging effects on the epigenomic features of brain is critical to understand brain functional decline and neurodegeneration. Single nucleus methylation sequencing was applied to brain regions of both male and female mouse at the age of 2, 9 and 18 months. We use these data to identify the epigenomic changes with aging in mouse brains.
• 🔗 查看原文

7. ⭐ GSE314260 人类躯干胚状体模型（hTEM）的单细胞和空间转录组学

• ✍️ 作者：未知作者
• 🏷️ 关键词：single-cell、spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributors : Tianming Wu ; Hao Yu ; Brian Wong ; Ling Xu ; Joaquim Vong ; Stephen DaltonSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Homo sapiensHuman embryoid models enable mechanistic studies of development and disease. We generated trunk embryoids from human pluripotent stem cells that recapitulate posterior trunk formation at Carnegie stage (CS) 8-10, with patterned anterior-posterior (A-P) and dorsal-ventral (D-V) axes. These self-organizing structures comprise a ventral notochord, dorsal neural tube, floor plate and bilateral somites. Genetic and chemical perturbations of SHH signaling confirmed the notochord’s central role in D-V patterning. Moreover, VANGL1/2 loss-of-function mutations recapitulated mouse phenotypes, including axial truncation and somite segmentation failure. This model enables detailed study of key developmental events that underlie posterior trunk formation and provides a promising platform for human disease modeling.
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8. ⭐ GSE314059 利用长读测序技术对小鼠脑进行单细胞和亚型特异性翻译分析 [scRNA-Seq, longread]

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing、single-cell、scRNA
• 📝 描述：Contributors : Samantha L Sison ; Federico Zampa ; Eric R Kofman ; Su Yeun Choi ; Pratibha Jagannatha ; Gene W Yeo ; Giordano LippiSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe brain displays the richest repertoire of post-transcriptional mechanisms regulating mRNA translation. Among these, alternative splicing has been shown to drive cell type specificity and, when disrupted, is strongly linked to neurological disorders. However, genome-wide measurements of mRNA translation with isoform-sensitivity at single-cell (sc) resolution have not been achieved. To address this, we deployed Ribo-STAMP (Surveying Ribosomal Targets by APOBEC-Mediated Profiling) coupled with long-read scRNA-sequencing (scRNA-seq) in the brain. We generated the first isoform-sensitive sc translatomes of the mouse hippocampus at postnatal day 25, discovering cell type-specific translation of 3,857 alternative transcripts across 1,641 genes, and identifying isoforms of the same genes undergoing differential translation within and across eight different cell types. We defined high and low translational states in CA1 and CA3 neurons, with synaptic and metabolic genes enriched in high states. Surprisingly, we found that CA3 exhibited higher basal translation compared to CA1, as confirmed by metabolic labeling of newly synthesized proteins and immunohistochemistry of translational machinery components. This accessible platform will expand our understanding of how cell type- and isoform-specific translation drives brain physiology and disease.
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9. ⭐ GSE308993 NSD2靶向逆转晚期前列腺癌的谱系可塑性和耐药性[批量RNA测序]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、resistance、RNA-seq
• 📝 描述：Contributors : Jia J Li ; Kristjan H Gretarsson ; Michael M ShenSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusTreatment with highly potent androgen receptor signaling inhibitors (ARSIs), such as enzalutamide and abiraterone promotes lineage plasticity in metastatic castration-resistant prostate cancer (mCRPC), which results in intra-tumor heterogeneity and emergence of mCRPC subtypes. The histological transformation from adenocarcinoma to aggressive neuroendocrine prostate cancer (CRPC-NE) has been associated with a loss of dependency on lineage-survival signals, leading to targeted drug resistance. Epigenomic reprogramming might be a fundamental driver of lineage plasticity. To determine CRPC-NE vulnerabilities, we have performed image-based screening using a small library of antibodies targeting different histone marks on CRPC-NE organoids derived from genetically engineered mice. We find that the histone mark H3K36me2 and the histone methyltransferase NSD2 (also known as MMSET/WHSC1) play important roles in maintaining the state of CRPC-NE. Knockout of NSD2 or ablation of H3K36me2 using H3.3K36M oncohistone reverted CRPC-NE to CRPC-AR-like phenotype. Simultaneous profiling of the transcriptome and epigenome from single cells collected from control (sgCtrl) and NSD2 knockout (sgNSD2) organoids, or from empty vector (EV) and H3.3K36M transduced organoids confirms the lineage reversal of treatment-resistant cells and maps the re-establishment of canonical AR signaling dependency. Moreover, H3K36me2 or NSD2 depleted mouse and human CRPC-NE organoids responded to enzalutamide treatment in vitro and in vivo, suggesting a restoration of ARSI sensitivity. Most importantly, a small molecule inhibitor of NSD2, which is similar to KTX-1001 (NCT05651932), in combination with enzalutamide leads to growth suppression or apoptosis of mouse and human CRPC-NE organoids, organoids of other CRPC subtypes and xenografts in vitro and in vivo. In conclusion, inhibition of NSD2 reverses lineage plasticity and reverts the state of treatment-resistant cells back into an ARSI-sensitive state. Thus, we suggest that the combination of NSD2 inhibition with AR inhibition may represent a novel therapeutic approach for patients with CRPC-NE and other CRPC subtypes.
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10. ⭐ GSE286020 SETD6 对 E2F1 的甲基化破坏了 BRD4-E2F1 的结合，并调节前列腺癌细胞中的基因调控 [ChIP-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、ChIP-seq、methylation
• 📝 描述：Contributors : Gizem T Ulu ; Margarita Kublanovsky ; Michal Feldman ; Sara Weirich ; Dan Levy ; Albert JeltschSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensThe SETD6 protein lysine methyltransferase has a role in the regulation of various cellular processes including cancer initiation and progression. It methylates several cellular proteins including K117 of the E2F1 transcription factor, but the functional consequences of this methylation event are unknown. In this study, the role of SETD6 mediated E2F1 methylation on the progression of prostate cancer was investigated. We identified distinct sets of genes that are bound and upregulated by methylated and unmethylated E2F1. Genes upregulated by methylated E2F1 lead to the negative regulation of cell migration, while genes upregulated by unmethylated E2F1 have roles in cell proliferation and apoptosis. BRD4 is known to bind E2F1 acetylated at K117 and K120. Here, we demonstrate that methylation of E2F1 at K117 prevents E2F1-BRD4 binding of in vitro and in cells establishing the molecular mechanism of the differential gene regulation by methylated and unmethylated E2F1 that depends on SETD6 activity.
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1. ASPEN——单细胞RNA测序中等位基因动态的稳健检测

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq
• 📝 描述：New ASPEN method enhances detection of allelic imbalance and variance in RNA sequencing data, revealing subtle gene regulation patterns in single cells…
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2. 阿尔茨海默病的线索可能就隐藏在我们的“垃圾”DNA中。

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer
• 📝 描述：CRISPRi screening with RNA sequencing maps functional DNA enhancers in human astrocytes, revealing gene control networks linked to Alzheimer’s disease…
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3. 一种新药有望在记忆丧失开始前阻止阿尔茨海默病的发展。

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer
• 📝 描述：New research suggests Alzheimer’s may start far earlier than previously thought, driven by a hidden toxic protein in the brain. Scientists found that an experimental drug, NU-9, blocks this early damage in mice and reduces inflammation linked to disease progression. The treatment was given before symptoms appeared, targeting the disease at its earliest stage. Researchers say this approach could reshape how Alzheimer’s is prevented and treated.
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4. 这种抗癌分子历经50年才研制成功。

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer
• 📝 描述：MIT scientists have achieved the first-ever lab synthesis of verticillin A, a complex fungal compound discovered in 1970. Its delicate structure stalled chemists for decades, despite differing from related molecules by only two atoms. With the synthesis finally complete, researchers created new variants that showed strong activity against a rare pediatric brain cancer. The breakthrough could unlock an entire class of previously unreachable cancer-fighting molecules.
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• GSE237191 NSD2靶向逆转晚期前列腺癌的谱系可塑性和耐药性[scRNA-seq]
• GSE314805 前列腺肿瘤免疫微环境在接受免疫治疗后发生变化，这些变化由出现抗肿瘤反应或免疫相关不良事件的患者分享
• GSE299434 表观遗传疗法联合 FACT 和 BET 抑制剂可重塑染色质并破坏弥漫性中线胶质瘤中的致癌转录 [Xenium]
• GSE272130 表观遗传疗法联合 FACT 和 BET 抑制剂可重塑染色质并破坏弥漫性中线胶质瘤中的致癌转录 [CUT&RUN]
• GSE313870 整合组学分析阐明了 ANKRD9 通过嘌呤代谢途径调控鸡原代成肌细胞 IMP 代谢的作用
• GSE314058 小鼠脑单细胞和亚型特异性翻译分析 [scRNA-seq]
• GSE308575 NSD2靶向逆转晚期前列腺癌的谱系可塑性和耐药性 [Cut&Tag]
• GSE292146 易于操作的小鼠 TNBC 模型捕捉到了异质性肿瘤免疫微环境以及对 PD-L1 阻断的适应性
• GSE291126 易于操作的小鼠 TNBC 模型捕捉到了异质性肿瘤免疫微环境以及对 PD-L1 阻断的适应性
• GSE290815 易于操作的小鼠 TNBC 模型捕捉了肿瘤免疫微环境的异质性以及对 PD-L1 阻断的适应性
• GSE286198 SETD6介导的E2F1甲基化破坏BRD4-E2F1结合并调节前列腺癌细胞中的基因表达
• GSE281998 细胞外基质蛋白1塑造肾脏纤维化微环境的代谢和空间动态
• GSE237197 NSD2靶向治疗逆转晚期前列腺癌的谱系可塑性和耐药性
• GSE237196 NSD2靶向逆转晚期前列腺癌的谱系可塑性和耐药性[snATAC-seq和多组snATAC-seq]
• GSE237195 NSD2靶向逆转晚期前列腺癌的谱系可塑性和耐药性[多组snRNA-seq]
• GSE314569 肠道菌群缺失对妊娠小鼠胎盘-脑轴的影响
• GSE306072 研究评估了用表观遗传抑制剂治疗的肿瘤细胞以及停药后肿瘤细胞的基因表达变化。
• GSE314020 有丝分裂细胞中转录组的全局稳定性 [RNA-Seq]
• GSE313694 脑膜瘤的空间转录组分析（Visium）
• GSE305964 大鼠盆腔神经损伤引起的神经源性膀胱的单细胞RNA测序
• GSE296159 深度靶向测序揭示原发性和复发性高级别浆液性卵巢癌之间的基因组差异
• GSE293642 日本血吸虫生殖发育过程中的单细胞RNA测序谱
• GSE289108 炎症脑中神经元发生 IFNγ 驱动的持续表观遗传改变和突触重塑 [ChIP-Seq]
• GSE289107 炎症脑中神经元发生 IFNγ 驱动的持续表观遗传改变和突触重塑 [ATAC-Seq]
• GSE288606 神经元在炎症脑中经历 IFNγ 驱动的持续表观遗传改变和突触重塑 [RNA-Seq]
• GSE293260 暴露于香烟烟雾的成年小鼠睾丸单细胞分析
• GSE280334 鉴定巨噬细胞依赖性Fcer1g+间充质细胞为伤口愈合过程中瘢痕形成的关键调节因子
• GSE275133 小鼠脑单细胞和亚型特异性翻译分析 [批量 RNA 测序]
• GSE270776 VHL 合成致死性筛选揭示 CBF-β 是 STING 的负调控因子（RNA-Seq）。
• GSE314162 杂交捕获 RNA-seq 定义了立克次体中基因表达的时间序列
• GSE297352 研究发现，可逆性细胞衰老中 RNA 加工缺陷和 ELOA 介导的转录延伸表明衰老是通过转录实现的。
• GSE285193 胰腺癌来源的细胞外囊泡对骨髓来源巨噬细胞的影响
• GSE284368 保留胚胎、胚外和胚泡生成潜能的原始人类多能干细胞的无饲养层培养 [RNA-Seq]
• GSE269948 研究发现，可逆性细胞衰老中 RNA 加工缺陷和 ELOA 介导的转录延伸表明衰老是通过转录实现的。
• GSE269718 研究发现，可逆性细胞衰老中 RNA 加工缺陷和 ELOA 介导的转录延伸表明衰老是通过转录实现的。
• GSE269717 研究发现，可逆性细胞衰老中 RNA 加工缺陷和 ELOA 介导的转录延伸提示衰老是通过转录实现的。
• GSE269715 研究发现，可逆性细胞衰老中 RNA 加工缺陷和 ELOA 介导的转录延伸提示衰老是通过转录实现的。
• GSE311598 成熟脂肪细胞中芳烃受体的激活不影响小鼠饮食诱导的肥胖 [scRNA-seq]
• GSE311153 成熟脂肪细胞中芳烃受体的激活不影响小鼠饮食诱导的肥胖 [RNA-seq]
• GSE264412 3例DIPG病例的批量RNA测序
• GSE314652 靶向 mTORC2 依赖性 AKT/FOXO1/RNF125 信号通路利用 c-MET 激活和 β-catenin 突变肝细胞癌的治疗弱点
• GSE314476 外源性天冬酰胺对结直肠肿瘤生长、17β-雌二醇水平和芳香化酶的性别特异性影响
• GSE314025 安格曼综合征猪模型额叶皮质单核RNA测序
• GSE314021 有丝分裂细胞中转录组的全局稳定性 [PALseq]
• GSE313978 膳食高纤维和N-氨甲酰谷氨酸通过调节乳酸杆菌、脂质代谢物和PI3K-Akt信号通路提高母猪繁殖性能
• GSE313951 祖先相关的IL-10信号传导和巨噬细胞活化调节基于PEG的微生理系统中成纤维细胞对氧化应激的反应
• GSE313865：扬子鲟单细胞图谱揭示活化石鱼类的演化
• GSE313693 脑膜瘤单核RNA测序
• GSE295714 机械敏感性 TRPV4 与 NF-κB 之间的新型串扰抑制肺部炎症
• GSE289109 炎症脑中神经元发生 IFNγ 驱动的持续表观遗传改变和突触重塑 [snRNA-Seq]