Stem Cell Reports最新文献_第4页

PML is crucial for neural stem cell differentiation, stress tolerance and mitochondrial integrity. PML对神经干细胞分化、应激耐受性和线粒体完整性至关重要。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-08-07 DOI: 10.1016/j.stemcr.2025.102598

Syrago Spanou, Takis Makatounakis, Elena Deligianni, Sofia Papanikolaou, Martina Samiotaki, Fabien Moretto, Christoforos Nikolaou, Joseph Papamatheakis, Androniki Kretsovali

{"title":"PML is crucial for neural stem cell differentiation, stress tolerance and mitochondrial integrity.","authors":"Syrago Spanou, Takis Makatounakis, Elena Deligianni, Sofia Papanikolaou, Martina Samiotaki, Fabien Moretto, Christoforos Nikolaou, Joseph Papamatheakis, Androniki Kretsovali","doi":"10.1016/j.stemcr.2025.102598","DOIUrl":"10.1016/j.stemcr.2025.102598","url":null,"abstract":"The tumor suppressor promyelocytic leukemia protein (PML) has important roles in brain development; however, the molecular and cellular pathways regulated by PML in neuronal cells remain largely unknown. To address this issue, we analyzed gene expression changes caused by loss of PML in neural stem cells. Our findings revealed that PML-deficient cells exhibited increased mTOR (mammalian target of rapamycin) pathway activation and protein translation, as well as impaired autophagy and proteasome activity, resulting in increased formation of aggregates and stress-induced death. Loss of PML disrupted mitochondrial integrity, leading to impaired respiration, membrane potential, morphology, and production of increased reactive oxygen species. These mitochondrial defects were caused by diminished PGC-1α expression and PPARγ (peroxisome proliferator-activated receptor gamma) signaling and could be reversed using a PPAR agonist. Together, our results indicate that PML is a critical regulator of neuronal survival and protection from stress. We propose that enhancing PML expression may offer therapeutic benefits in neurological disorders.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102598"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ependymal and neural stem cells are close relatives. 室管膜干细胞和神经干细胞是近亲。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-07-03 DOI: 10.1016/j.stemcr.2025.102574

Georgia Lokka, Anna Chantzara, Zoi Lygerou, Stavros Taraviras

引用次数: 0

Establishment of neuronal and glial competence of neural stem cells requires distinct enzymatic activities of TET enzymes. 神经干细胞的神经元和胶质能力的建立需要不同的TET酶活性。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-07-31 DOI: 10.1016/j.stemcr.2025.102595

Blake C Ebert, Ian C MacArthur, Harmony C Ketchum, Michael Musheev, Christof Niehrs, Masako Suzuki, Meelad M Dawlaty

{"title":"Establishment of neuronal and glial competence of neural stem cells requires distinct enzymatic activities of TET enzymes.","authors":"Blake C Ebert, Ian C MacArthur, Harmony C Ketchum, Michael Musheev, Christof Niehrs, Masako Suzuki, Meelad M Dawlaty","doi":"10.1016/j.stemcr.2025.102595","DOIUrl":"10.1016/j.stemcr.2025.102595","url":null,"abstract":"Ten-eleven translocation (TET1/2/3) enzymes are expressed in neural stem cells (NSCs). They iteratively oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). The significance of hydroxymethylation (i.e., 5hmC) versus formylation and carboxylation (i.e., active demethylation) is undefined. We generated NSCs lacking only TET formylation and carboxylation activities (Tet-TFoCa) and compared them to NSCs lacking all three TET activities (Tet-TMut). Tet-TFoCa NSCs could differentiate into neurons but not into glial cells, while Tet-TMut NSCs could not form either cell type. Mechanistically, neuronal genes retained 5hmC at their enhancers in Tet-TFoCa NSCs and were expressed normally, consistent with the ability of these cells to form neurons. In contrast, enhancers of glial genes were hypermethylated in both Tet-TFoCa and Tet-TMut NSCs underpinning downregulation of these genes and the glial block in these cells. Our findings implicate TET-driven hydroxymethylation in establishing NSC neuronal competence and formylation and carboxylation in defining NSC glial competence.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102595"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toti: An integrated multi-omics database to decipher the epigenetic regulation of gene expression in totipotent stem cells. Toti：一个集成的多组学数据库，用于破译全能干细胞中基因表达的表观遗传调控。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-08-21 DOI: 10.1016/j.stemcr.2025.102605

Yi Chai, Ruiying Zhang, Shunze Jia, Danfei Zhu, Siyi Chen, Shuai Liu, Na Kong, Xudong Fu, Xin Sheng

{"title":"Toti: An integrated multi-omics database to decipher the epigenetic regulation of gene expression in totipotent stem cells.","authors":"Yi Chai, Ruiying Zhang, Shunze Jia, Danfei Zhu, Siyi Chen, Shuai Liu, Na Kong, Xudong Fu, Xin Sheng","doi":"10.1016/j.stemcr.2025.102605","DOIUrl":"10.1016/j.stemcr.2025.102605","url":null,"abstract":"Totipotent stem cells (TSCs), the origin of mammalian life and the foundation of early embryogenesis, possess the highest differentiation capacity and extensive developmental potential. However, none of the existing embryonic databases have provided epigenetic and transcriptomic resources on totipotency, greatly limiting our understanding of its establishment and exit mechanisms. Here, we present Toti, a pioneering multi-omics database developed to investigate transcriptional and epigenetic factors governing totipotency, encompassing in vivo, in vitro, and genome-edited human and mouse embryonic TSCs, TSC-like cells, pluripotent stem cells, and embryos spanning preimplantation stages, with a total of 8,284 samples. Toti enables flexible keyword-based search, comparative visualization of transcriptomic and epigenetic features, motif and pathway enrichment analysis across diverse cell types, and single-cell resolution investigation of totipotency by offering Search, Browse, and Analysis modules, available at http://toti.zju.edu.cn/. Toti thus serves as a valuable resource for exploring the molecular underpinnings of totipotency.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102605"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TAOK2 drives opposing cilia length deficits in 16p11.2 deletion and duplication carriers. 在16p11.2缺失和重复携带者中，TAOK2驱动相反的纤毛长度缺陷。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-08-28 DOI: 10.1016/j.stemcr.2025.102608

Sujin Byeon, Amy Ferreccio, Moira Cornell, Juan A Oses-Prieto, Aditi Deshpande, Siri Manvi, Alison Blencowe, Lauren A Weiss, Alma L Burlingame, Smita Yadav

{"title":"TAOK2 drives opposing cilia length deficits in 16p11.2 deletion and duplication carriers.","authors":"Sujin Byeon, Amy Ferreccio, Moira Cornell, Juan A Oses-Prieto, Aditi Deshpande, Siri Manvi, Alison Blencowe, Lauren A Weiss, Alma L Burlingame, Smita Yadav","doi":"10.1016/j.stemcr.2025.102608","DOIUrl":"10.1016/j.stemcr.2025.102608","url":null,"abstract":"Deletion and duplication of the 16p11.2 genomic locus are associated with opposing changes in brain size. To determine cellular mechanisms that underlie these opposing phenotypes, we performed quantitative phosphoproteomic analyses of induced pluripotent stem cells (iPSCs)-derived neural progenitor cells (NPCs) obtained from unaffected individuals, 16p11.2 deletion, and 16p11.2 duplication carriers. Differentially phosphorylated proteins were enriched in centrosomal and cilia proteins. Deletion NPCs showed longer primary cilium compared to unaffected individuals, while stunted cilia were observed in duplication NPCs. Through cellular screens in NPCs, we determined the contribution of genes within the 16p11.2 locus to cilium length. Protein kinase TAOK2 and phosphatase PPP4C were found to regulate primary cilia length. NPCs lacking TAOK2 exhibited elongated cilia, aberrant IFT88 and pericentrin (PCNT) accumulation, and were impaired in sonic hedgehog (SHH) signaling. These findings implicate aberrant cilia length in the pathophysiology of 16p11.2 copy number variation and establish TAOK2 kinase as a regulator of primary cilium length.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102608"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineering human neuronal diversity: Morphogens and stem cell technologies for neurodevelopmental biology. 工程人类神经元多样性：神经发育生物学的形成因子和干细胞技术。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 DOI: 10.1016/j.stemcr.2025.102615

Soraya Scuderi, Nagham Khouri-Farah, Riya Rauthan, Abhiram Natu, Hantao Wang, Alex Nelson, Alexandre Jourdon, Flora M Vaccarino

引用次数: 0

Distinct roles of TET-mediated cytosine oxidation in neural stem cell fate decisions. tet介导的胞嘧啶氧化在神经干细胞命运决定中的独特作用。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 DOI: 10.1016/j.stemcr.2025.102614

Oren Ram

引用次数: 0

Embracing the heterogeneity of neural stem cells in the subventricular zone. 拥抱室管膜下区神经干细胞的异质性。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-03-20 DOI: 10.1016/j.stemcr.2025.102452

Stefania Apostolou, Vanessa Donega

引用次数: 0

Three-dimensional co-culturing reveals human stem cell-derived somatostatin interneurons with subclass expression. 三维共培养揭示人干细胞来源的生长抑素中间神经元亚类表达。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 DOI: 10.1016/j.stemcr.2025.102634

Andreas Bruzelius, Christina-Anastasia Stamouli, Anna-Lena Hölldobler, Constanza Aretio-Medina, Efrain Cepeda-Prado, Edoardo Sozzi, Germán Ramos Passarello, Gianluigi Nocera, Jessica Giacomoni, Victor Olariu, Daniella Rylander Ottosson

{"title":"Three-dimensional co-culturing reveals human stem cell-derived somatostatin interneurons with subclass expression.","authors":"Andreas Bruzelius, Christina-Anastasia Stamouli, Anna-Lena Hölldobler, Constanza Aretio-Medina, Efrain Cepeda-Prado, Edoardo Sozzi, Germán Ramos Passarello, Gianluigi Nocera, Jessica Giacomoni, Victor Olariu, Daniella Rylander Ottosson","doi":"10.1016/j.stemcr.2025.102634","DOIUrl":"10.1016/j.stemcr.2025.102634","url":null,"abstract":"Cortical interneuron deficiencies, particularly involving the somatostatin (SST) subtypes, contribute to neurological and neuropsychiatric disorders. These interneurons are difficult to derive in vitro from human embryonic stem cells (hESCs) due to their late embryonic development and dependence on glial interaction. To this end, we developed a three-dimensional co-culture model of hESC-derived neurons, enabling long-term development, functional maturity, and neuron-glial interaction. Under these conditions, hESCs successfully differentiated into functional GABAergic interneurons expressing the SST gene and protein within 50 days. Single-nuclei RNA sequencing revealed transcripts for SST subclasses, including Martinotti, non-Martinotti, and long-projecting neurons, that have not yet been described for hESC cultures. Upon injection into forebrain organoids, the interneuron progenitors spread and functionally matured while retaining their SST subclass identities, suggesting cell-intrinsic fate specification. Our in vitro model provides a robust platform for studying human SST interneurons, offering new avenues for investigating their role in health and disease.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":"20 9","pages":"102634"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neural stem cells of the subventricular zone: A potential stem cell pool for brain repair in Parkinson's disease. 脑室下区神经干细胞：帕金森病脑修复的潜在干细胞库

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-06-12 DOI: 10.1016/j.stemcr.2025.102533

Marloes Verkerke, Maarten H Werkman, Vanessa Donega

引用次数: 0