详细内容（前10条）

1. ⭐ GSE306327 瘢痕相关的内皮-星状细胞串扰驱动 MASH 中的纤维化消退 [空间转录组学]

• ✍️ 作者：未知作者
• 🏷️ 关键词：spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributor : Kenneth LiSeries Type : OtherOrganism : Mus musculusFibrosis, or scarring, can affect many organs including liver, lung, heart, kidney, intestines etc. and contributes to ~40% of mortality in the industrialized world. Unlike other organs, fibrosis in the liver typically resolves when the source of injury is extinguished. Elucidating the molecular mechanisms that underlie spontaneous fibrosis resolution may lead to novel antifibrotic strategies. In this study we established a robust mouse model of fibrosis regression in MASH (Metabolic dysfunction-Associated Steatohepatitis), a highly prevalent chronic liver disease worldwide, and performed single cell and in situ molecular profiling to define the molecular drivers of fibrosis regression. As fibrosis regressed, inflammatory cell numbers decreased and endothelial cell (EC) numbers increased. Prediction of cell-cell communication using the Calligraphy pipeline identified a Wnt9b-Sfrp2 crosstalk that emerged as fibrosis resolved. To investigate the Wnt9b-Sfrp2 crosstalk as a driver of fibrosis resolution we treated mice with recombinant SFRP2, a WNT inhibitor, which attenuated spontaneous fibrosis regression compared to vehicle-treated mice. Using single nucleus RNA sequencing, we identified a subset of liver ECs termed ‘Endo4’, as the source of Wnt9b. Immunostaining of the Endo4 marker VWF using tissue clearing and 3D imaging identified VWF+ vasculature surrounded by activated hepatic stellate cells (HSCs) that penetrated deep into the fibrotic septa, establishing them as de facto scar-associated ECs. Functionally, using a novel in situ protease activity-based probes, prominent serine protease activity was found to be co-localized with both scar-associated Endo4 ECs and HSCs. In summary, WNT-dependent endo-stellate crosstalk within the fibrotic niche represents a novel regulatory node in murine MASH fibrosis regression and a promising therapeutic target.
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2. GSE313892 CD276-DM1 抗体药物偶联物与 cmLumiOpto 基因疗法治疗三阴性乳腺癌。

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、antibody
• 📝 描述：Series Type : Expression profiling by high throughput sequencingOrganism : Mus musculusTriple-negative breast cancer (TNBC) is a highly aggressive subtype characterized by resistance to chemotherapy, elevated metastatic potential, and frequent relapse. This study investigated the therapeutic impact of combining an antibody-drug conjugate (ADC) with mitochondria-targeted gene therapy. A CD276-directed monoclonal antibody conjugated to mertansine when paired with cmLumiOpto gene therapy, exhibited potent synergistic activity across three TNBC cell lines, impairing mitochondrial function and amplifying tumor-associated cytokine responses. In vivo experiments further demonstrated that the ADC/cmLumiOpto combination effectively suppressed metastasis in metastatic models and achieved high tumor growth inhibition in patient-derived xenograft mouse models. Mechanistic studies revealed that this dual approach downregulated metastatic signaling pathways, disrupted the tumor microenvironment, and triggered apoptosis. Importantly, histological assessments of normal tissues and body weight monitoring indicated negligible toxicity. Collectively, these findings highlight the therapeutic promise of CD276-targeted ADCs combined with gene therapy as a strategy for treating TNBC.
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3. GSE295221 无义介导的 mRNA 衰变协调神经元迁移和皮层分层，同时调节 reelin 和纤毛基因调控网络（RNA 测序）

• ✍️ 作者：未知作者
• 🏷️ 关键词：Neuronal、RNAseq
• 📝 描述：Contributors : Lin Lin ; Naoto Kubota ; Sika ZhengSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusNonsense-mediated mRNA decay (NMD) is associated with various neurodevelopmental disorders. Here, we demonstrate that NMD, mediated by UPF2, previously not linked to cortical organization, is indispensable for neuronal migration and cortical lamination. Conditional deletion of Upf2 in radial glial cells delays neuronal migration and disrupts cortical lamination. Trp53 knockout rescues microcephaly from Upf2 deficiency but cannot rescue lamination defects, showing that UPF2’s role in neuronal migration is uncoupled from its regulation of cell cycle and independent of p53. UPF2 deficiency downregulates key neuronal migration genes in the Reelin signaling pathway and microtubule assembly (e.g., Dab1, Lrp8, Tubb2b, Tuba1a), partly through upregulation of the transcriptional repressor Ino80. Additionally, NMD inhibition causes widespread upregulation of ciliary genes. Ectopic expression of Foxj1, a master regulator of ciliary genes and NMD target, impedes neuronal migration, mimicking the Upf2 knockout phenotype. Therefore, NMD is a central post-transcriptional mechanism that coordinates migration and ciliary gene networks crucial for cortical structure development, providing insight into how NMD dysfunction contributes to neurodevelopmental disorders.
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4. GSE311977 脓毒症小鼠脑组织单细胞测序数据

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing、single-cell
• 📝 描述：Contributors : Jiayu Song ; Qile Ye ; Rong Tang ; Yuwen Wang ; Mengmeng Zhang ; Rui Zhao ; Jie LiuSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusTo explore the specific molecular mechanisms underlying brain injury caused by sepsis, we conducted single-cell transcriptomic analysis on mouse brain tissues. In the experimental group, mice were administered 54 mg/kg of lipopolysaccharide (LPS) via intraperitoneal injection to establish a mouse model of sepsis-associated encephalopathy (SAE). In the control group, mice received an equivalent volume of phosphate-buffered saline (PBS).
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5. GSE228309 RNA测序转录组分析：创伤性脑损伤后5天病灶至病灶周围皮质的转录组分析

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing、transcriptome
• 📝 描述：Contributors : Michael K Schäfer ; Matthias Klein ; Irmgard TegederSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusC57BL6/N male mice (14-week-old) were subjected to a controlled cortical impact (CCI) to induce a unilateral traumatic brain injury (TBI). After surgery, mice were treated and monitored for 5 days after TBI (5 dpi). There were four treatment groups, each consisting in five male mice (n = 5 per group). Group-1 received the CSF1R antagonist, PLX3397 (pexidartinib) via food pellets (290 mg per kilogram of pellets, feeding at libitum). Group-2 received the interleukin-1 receptor antagonist (IL1RA), anakinra (100 mg/kg body weight subcutaneously at 5 min, 24h, 48h, and 72h after CCI). Group-3 received both PLX3397 and anakinra (PLX3397+anakinra), and Group-4 got vehicle p.o. and s.c.. A control group was subjected to sham-surgy (n = 4)which included anesthesia, skin incision and suture but no skull penetration. PLX3397 leads to a depletion of microglial cells which was confirmed by immunohistochemistry. Lesional to perilesional cortical tissue was obtained 5 dpi (Brgema: +0.64 mm to -2.86 mm) to assess differential gene and transcript expression, microglia depletion and cortical reorganization. Behavioral scores for well-being and motor functions were obatined repeatedly during the observation time. Histology of brain lesion size, indices of neuronal damage and neuroinflammation were obtained at 5 days after TBI. Neuroinflammatory markers tended to be lower in PLX3397 treated mice, there was almost no effects of anakinra alone but inflammation and lesion volume were strongly reduced in the PLX3397+anakinra group, which was associated with better neurological outcome suggesting synergistic effects of PLX3997 and anakinra after TBI.
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6. GSE305330 瘢痕相关内皮-星状细胞相互作用驱动 MASH 中的纤维化消退 [scRNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：scRNA
• 📝 描述：Contributor : Kenneth LiSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusFibrosis, or scarring, can affect many organs including liver, lung, heart, kidney, intestines etc. and contributes to ~40% of mortality in the industrialized world. Unlike other organs, fibrosis in the liver typically resolves when the source of injury is extinguished. Elucidating the molecular mechanisms that underlie spontaneous fibrosis resolution may lead to novel antifibrotic strategies. In this study we established a robust mouse model of fibrosis regression in MASH (Metabolic dysfunction-Associated Steatohepatitis), a highly prevalent chronic liver disease worldwide, and performed single cell and in situ molecular profiling to define the molecular drivers of fibrosis regression. As fibrosis regressed, inflammatory cell numbers decreased and endothelial cell (EC) numbers increased. Prediction of cell-cell communication using the Calligraphy pipeline identified a Wnt9b-Sfrp2 crosstalk that emerged as fibrosis resolved. To investigate the Wnt9b-Sfrp2 crosstalk as a driver of fibrosis resolution we treated mice with recombinant SFRP2, a WNT inhibitor, which attenuated spontaneous fibrosis regression compared to vehicle-treated mice. Using single nucleus RNA sequencing, we identified a subset of liver ECs termed ‘Endo4’, as the source of Wnt9b. Immunostaining of the Endo4 marker VWF using tissue clearing and 3D imaging identified VWF+ vasculature surrounded by activated hepatic stellate cells (HSCs) that penetrated deep into the fibrotic septa, establishing them as de facto scar-associated ECs. Functionally, using a novel in situ protease activity-based probes, prominent serine protease activity was found to be co-localized with both scar-associated Endo4 ECs and HSCs. In summary, WNT-dependent endo-stellate crosstalk within the fibrotic niche represents a novel regulatory node in murine MASH fibrosis regression and a promising therapeutic target.
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7. GSE310518 bacTRAP 分析野生型对照组小鼠五个脑区和阿尔茨海默病小鼠模型海马区星形胶质细胞的表达谱

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer
• 📝 描述：Contributor : Ana MilosevicSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusWe experimentally generated astrocyte gene expression profiles in five major brain regions in mouse: prefrontal cortex (P), hippocampus (H), amygdala (A), caudate nucleus (C) and ventral striatum (V) (Figure 1A, Methods), with more than three biological replicates in each region. To derive the differences between the regional transcriptional profiles, we utilized TRAP-seq, a method that enables detailed profiling of actively translated mRNA, rather than just transcribed mRNA, thus better capturing the functional state of the cell. This approach enables us to generate ex vivo region-specific astrocyte signatures.
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8. GSE295222 无义介导的 mRNA 衰变协调神经元迁移和皮层分层，同时调节 reelin 和纤毛基因调控网络（snRNAseq）

• ✍️ 作者：未知作者
• 🏷️ 关键词：Neuronal
• 📝 描述：Contributors : Lin Lin ; Naoto Kubota ; Sika ZhengSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusNonsense-mediated mRNA decay (NMD) is associated with various neurodevelopmental disorders. Here, we demonstrate that NMD, mediated by UPF2, previously not linked to cortical organization, is indispensable for neuronal migration and cortical lamination. Conditional deletion of Upf2 in radial glial cells delays neuronal migration and disrupts cortical lamination. Trp53 knockout rescues microcephaly from Upf2 deficiency but cannot rescue lamination defects, showing that UPF2’s role in neuronal migration is uncoupled from its regulation of cell cycle and independent of p53. UPF2 deficiency downregulates key neuronal migration genes in the Reelin signaling pathway and microtubule assembly (e.g., Dab1, Lrp8, Tubb2b, Tuba1a), partly through upregulation of the transcriptional repressor Ino80. Additionally, NMD inhibition causes widespread upregulation of ciliary genes. Ectopic expression of Foxj1, a master regulator of ciliary genes and NMD target, impedes neuronal migration, mimicking the Upf2 knockout phenotype. Therefore, NMD is a central post-transcriptional mechanism that coordinates migration and ciliary gene networks crucial for cortical structure development, providing insight into how NMD dysfunction contributes to neurodevelopmental disorders.
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9. GSE314005 TRIM40 通过 PKN2 泛素化驱动病理性心脏肥大和心力衰竭

• ✍️ 作者：未知作者
• 🏷️ 关键词：cardiac
• 📝 描述：Contributors : Risheng Zhao ; Mengyang WangSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusPathological cardiac hypertrophy is a key predisposing factor for heart failure (HF). This study investigates the role of the E3 ubiquitin ligase Tripartite Motif-Containing 40 (TRIM40) in cardiac hypertrophy. Using TRIM40 knockout (TRIM40-/-) and cardiac-specific overexpressing mice, pathological hypertrophy was induced by angiotensin II (Ang II) infusion or transverse aortic constriction (TAC). Results demonstrated that TRIM40 expression was upregulated in hypertrophic hearts. TRIM40 deficiency attenuated cardiac hypertrophy and dysfunction, whereas its overexpression exacerbated pathological remodeling. Mechanistically, TRIM40 binds Protein Kinase N2 (PKN2) via its B-box domain, promoting K63-linked ubiquitination at cysteine 29 that enhances PKN2 phosphorylation at Ser815 and activates downstream signaling. Pharmacological inhibition of PKN2 attenuated cardiac remodeling induced by TRIM40 overexpression. These findings indicate that TRIM40 promotes cardiac hypertrophy through K63-linked ubiquitination and activation of PKN2, identifying TRIM40 as a potential therapeutic target for HF.
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10. GSE313561 RNA-seq 数据来自经 TSK 治疗的糖尿病肾病大鼠肾脏。

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq
• 📝 描述：Contributors : Na Zhao ; Ran Wei ; Nuan Wen ; Jian Ma ; Xicheng Jiang ; Huijun Chen ; Bingmei Wang ; Chuwen Feng ; Lei Zheng ; Shanshan Zheng ; Wei Zhou ; Zeyu YuSeries Type : Expression profiling by high throughput sequencingOrganism : Rattus norvegicusTSK (TangShenKang) is a compound traditional Chinese medicine. To explore the core corresponding program of this medicine acting on diabetic kidneys, RNA-seq was conducted on rats kidney tissues under different treatments in this study. Specifically, this experiment was divided into three groups (6 rats in each group) : Normal control group (Ctrl) , DN model group, treatment group.
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• GSE295270 NONO 缺陷损害 HOXA1 染色质结合，从而破坏人类 iPSC 中 Wnt 驱动的心肌细胞分化 [ChIP-Seq]
• GSE192441 肺部 B 淋巴细胞可改善阿尔茨海默病样神经病理学