Stem Cell Reports最新文献_第8页

An acidic residue within the OCT4 dimerization interface of SOX17 is necessary and sufficient to overcome its pluripotency-inducing activity. SOX17的OCT4二聚化界面内的酸性残基是克服其多能诱导活性的必要和充分条件。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-11 Epub Date: 2025-02-06 DOI: 10.1016/j.stemcr.2025.102398

Sik Yin Ho, Haoqing Hu, Derek Hoi Hang Ho, Allan Patrick Stephane Renom, Shi Wing Yeung, Freya Boerner, Mingxi Weng, Andrew Paul Hutchins, Ralf Jauch

{"title":"An acidic residue within the OCT4 dimerization interface of SOX17 is necessary and sufficient to overcome its pluripotency-inducing activity.","authors":"Sik Yin Ho, Haoqing Hu, Derek Hoi Hang Ho, Allan Patrick Stephane Renom, Shi Wing Yeung, Freya Boerner, Mingxi Weng, Andrew Paul Hutchins, Ralf Jauch","doi":"10.1016/j.stemcr.2025.102398","DOIUrl":"10.1016/j.stemcr.2025.102398","url":null,"abstract":"SOX17 directs the differentiation toward endoderm and acts as a human germline specifier. We previously found that the replacement of glutamate at position 57 of the high-mobility group (HMG) box with the basic lysine residue in SOX2 alters interactions with OCT4 and turns SOX17 into a pluripotency factor. Here, we systematically interrogated how mutations at this critical position affect the cellular reprogramming activity of SOX17 in mouse and human. We found that most mutations turn SOX17 into a pluripotency factor regardless of their biophysical properties except for acidic residues and proline. The conservative mutation to an aspartate allows the SOX17E57D protein to maintain a self-renewing endodermal state. We showed that only the glutamate in the wild-type protein blocks the formation of an SOX17/OCT4 dimer at composite DNA elements in pluripotency enhancers. Insights into how modifications of an ultra-conserved residue affect functions of developmental transcription factors provide avenues to advance cell fate engineering.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102398"},"PeriodicalIF":5.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370984","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

Autism- and intellectual disability-associated MYT1L mutation alters human cortical interneuron differentiation, maturation, and physiology. 自闭症和智力残疾相关的MYT1L突变改变了人类皮层中间神经元的分化、成熟和生理。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-11 Epub Date: 2025-02-27 DOI: 10.1016/j.stemcr.2025.102421

Ramachandran Prakasam, Julianna Determan, Gareth Chapman, Mishka Narasimhan, Renata Shen, Maamoon Saleh, Komal Kaushik, Paul Gontarz, Kesavan Meganathan, Bilal Hakim, Bo Zhang, James E Huettner, Kristen L Kroll

{"title":"Autism- and intellectual disability-associated MYT1L mutation alters human cortical interneuron differentiation, maturation, and physiology.","authors":"Ramachandran Prakasam, Julianna Determan, Gareth Chapman, Mishka Narasimhan, Renata Shen, Maamoon Saleh, Komal Kaushik, Paul Gontarz, Kesavan Meganathan, Bilal Hakim, Bo Zhang, James E Huettner, Kristen L Kroll","doi":"10.1016/j.stemcr.2025.102421","DOIUrl":"10.1016/j.stemcr.2025.102421","url":null,"abstract":"Myelin transcription factor 1 like (MYT1L) is a neuronal transcription factor highly expressed in the developing and adult brain, and, while pathogenic MYT1L mutations cause neurodevelopmental disorders, these have not been characterized in human models of neurodevelopment. Here, we modeled the consequences of pathogenic MYT1L mutation using human stem cell-derived cortical neurons, demonstrating that MYT1L mutation alters the differentiation trajectory, increasing neuronal gene expression, morphological complexity, and synapse production. We also examined consequences of MYT1L mutation in mature cortical interneurons, identifying hallmarks of impaired neuronal identity and maturation and correspondingly altered channel expression and electrophysiological properties. Finally, by defining MYT1L genome-wide occupancy in cortical interneurons, we identified direct MYT1L targets likely to mediate these phenotypes. Together, this work elucidates new MYT1L requirements for human cortical interneuron development and demonstrates how pathogenic MYT1L mutation perturbs this developmental program, contributing to the etiology of neurodevelopmental disorders.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102421"},"PeriodicalIF":5.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531793","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

Tracking and mitigating imprint erasure during induction of naive human pluripotency at single-cell resolution. 以单细胞分辨率跟踪和减轻诱导幼稚人类多能性过程中的印记擦除。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-11 Epub Date: 2025-02-13 DOI: 10.1016/j.stemcr.2025.102419

Laura A Fischer, Brittany Meyer, Monica Reyes, Joseph E Zemke, Jessica K Harrison, Kyoung-Mi Park, Ting Wang, Harald Jüppner, Sabine Dietmann, Thorold W Theunissen

{"title":"Tracking and mitigating imprint erasure during induction of naive human pluripotency at single-cell resolution.","authors":"Laura A Fischer, Brittany Meyer, Monica Reyes, Joseph E Zemke, Jessica K Harrison, Kyoung-Mi Park, Ting Wang, Harald Jüppner, Sabine Dietmann, Thorold W Theunissen","doi":"10.1016/j.stemcr.2025.102419","DOIUrl":"10.1016/j.stemcr.2025.102419","url":null,"abstract":"Naive human pluripotent stem cells (hPSCs) model the pre-implantation epiblast. However, parent-specific epigenetic marks (imprints) are eroded in naive hPSCs, which represents an important deviation from the epiblast in vivo. To track the dynamics of imprint erasure during naive resetting in real time, we established a dual-colored fluorescent reporter at both alleles of the imprinted SNRPN locus. During primed-to-naive resetting, SNRPN expression becomes biallelic in most naive cells, and biallelic SNRPN expression is irreversible upon re-priming. We utilized this live-cell reporter to evaluate chemical and genetic strategies to minimize imprint erasure. Decreasing the level of MEK/ERK inhibition or overexpressing the KRAB zinc-finger protein ZFP57 protected a subset of imprints during naive resetting. Combining these two strategies protected imprint levels to a further extent than either strategy alone. This study offers an experimental tool to track and enhance imprint stability during transitions between human pluripotent states in vitro.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102419"},"PeriodicalIF":5.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426341","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

Comment on "MSCohi-O lenses for long-term retention of mesenchymal stem cells on ocular surface as a therapeutic approach for chronic ocular graft-versus-host disease". 对“MSCohi-O晶状体长期保留眼表间充质干细胞作为慢性眼移植物抗宿主病的治疗方法”的评论。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-11 Epub Date: 2025-02-06 DOI: 10.1016/j.stemcr.2025.102401

Xinxin Yu, Shuai Huang, Yizhuo Zhao, Aijun Deng, Lusheng Ma

引用次数: 0

A Chemically Defined Feeder-free System for the Establishment and Maintenance of the Human Naive Pluripotent State. 建立和维持人类原始多能状态的化学定义的无馈源系统。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-11 Epub Date: 2025-02-28 DOI: 10.1016/j.stemcr.2025.102446

Iwona Szczerbinska, Kevin Andrew Uy Gonzales, Engin Cukuroglu, Muhammad Nadzim Bin Ramli, Bertha Pei Ge Lee, Cheng Peow Tan, Cheng Kit Wong, Giulia Irene Rancati, Hongqing Liang, Jonathan Göke, Huck-Hui Ng, Yun-Shen Chan

引用次数: 0

An efficient, non-viral arrayed CRISPR screening platform for iPSC-derived myeloid and microglia models. 一个高效的，非病毒排列的CRISPR筛选平台，用于ipsc衍生的髓细胞和小胶质细胞模型。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-11 Epub Date: 2025-02-20 DOI: 10.1016/j.stemcr.2025.102420

Sonja Meier, Anne Sofie Gry Larsen, Florian Wanke, Nicolas Mercado, Arianna Mei, Livia Takacs, Eva Suszanna Mracsko, Ludovic Collin, Martin Kampmann, Filip Roudnicky, Ravi Jagasia

引用次数: 0

Clonal lineage tracing and transcriptomics of cortical progenitor populations reveal maintenance of differentiation potential. 大脑皮层祖细胞的克隆谱系追踪和转录组学揭示了分化潜能的维持。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-11 Epub Date: 2025-02-13 DOI: 10.1016/j.stemcr.2025.102418

Danyon Harkins, Shawar Ali, Teodora Tockovska, Sara Ciganovic, Daniela Lozano Casasbuenas, Samuel Watanabe, Stephanie Ouzikov, Scott A Yuzwa

{"title":"Clonal lineage tracing and transcriptomics of cortical progenitor populations reveal maintenance of differentiation potential.","authors":"Danyon Harkins, Shawar Ali, Teodora Tockovska, Sara Ciganovic, Daniela Lozano Casasbuenas, Samuel Watanabe, Stephanie Ouzikov, Scott A Yuzwa","doi":"10.1016/j.stemcr.2025.102418","DOIUrl":"10.1016/j.stemcr.2025.102418","url":null,"abstract":"Postnatal neocortical development is a complex period wherein radial glial progenitors (RGPs) complete excitatory neurogenesis and transition to the production of glia. Here, we take advantage of a multi-layered lineage tracing tool pbacBarcode, to examine the contributions of individual cortical RGPs to the postnatal cortex. We reveal that some individual cortical RGPs are multipotent and give rise to olfactory bulb interneurons, astrocytes, and oligodendrocytes in a ∼2:1:1 ratio. We provide evidence that differentiation potential into terminal cell types is maintained as late as post-natal day (P)4, suggesting that a population decline model, as opposed to cell fate restriction, underlies postnatal neocortical development. Moreover, a pool of proliferative intermediary cells, which may represent a multipotent postnatal intermediate progenitor cell population, may contribute to the production of the three major cell types. Lastly, we examine RGP postnatal contribution to oligodendrocytes and show that oligodendrocyte progenitor founder cell production by cortical RGPs is largely complete by P3.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102418"},"PeriodicalIF":5.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426338","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

High-dose radiation preferentially induces the clonal expansion of hematopoietic progenitor cells over mature T and B cells in mouse bone marrow. 高剂量辐射优先诱导小鼠骨髓中造血祖细胞克隆扩增超过成熟的T细胞和B细胞。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-11 Epub Date: 2025-02-27 DOI: 10.1016/j.stemcr.2025.102423

Kengo Yoshida, Munechika Misumi, Kanya Hamasaki, Seishi Kyoizumi, Yasunari Satoh, Tatsuaki Tsuruyama, Arikuni Uchimura, Yoichiro Kusunoki

{"title":"High-dose radiation preferentially induces the clonal expansion of hematopoietic progenitor cells over mature T and B cells in mouse bone marrow.","authors":"Kengo Yoshida, Munechika Misumi, Kanya Hamasaki, Seishi Kyoizumi, Yasunari Satoh, Tatsuaki Tsuruyama, Arikuni Uchimura, Yoichiro Kusunoki","doi":"10.1016/j.stemcr.2025.102423","DOIUrl":"10.1016/j.stemcr.2025.102423","url":null,"abstract":"Radiation induces clonal hematopoiesis (CH) involving high-frequency somatic mutations in hematopoietic cells. However, the effects of radiation on clonal expansion of hematopoietic progenitor cells and lymphocytes remain elusive. Here, we investigate CH mutations and T cell receptor (TCR) and B cell receptor (BCR) sequences within the bone marrow cells of mice 18 months after irradiation (3 Gy) and age-matched controls. Two to six CH mutations were identified in the irradiated mice (N = 5), while only one of the four control mice carried a CH mutation. These CH mutations detected in the bone marrow were also identified in the splenic CD11b+ myeloid cell population. Meanwhile, the cumulative size of the ten largest TCR and BCR clones, as well as their clonality, did not differ significantly between irradiated and control mice. Our findings suggest that radiation preferentially induces clonal expansion of hematopoietic progenitor cells over mature lymphocytes in the bone marrow.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102423"},"PeriodicalIF":5.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531795","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

ERK phosphorylates ESRRB to regulate the self-renewal and differentiation of mouse embryonic stem cells. ERK磷酸化ESRRB调控小鼠胚胎干细胞的自我更新和分化。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-11 Epub Date: 2025-02-06 DOI: 10.1016/j.stemcr.2025.102397

Xiaowei Duan, Qingye Zhang, Lulu Gao, Bin Ling, Xiaoling Du, Lingyi Chen

{"title":"ERK phosphorylates ESRRB to regulate the self-renewal and differentiation of mouse embryonic stem cells.","authors":"Xiaowei Duan, Qingye Zhang, Lulu Gao, Bin Ling, Xiaoling Du, Lingyi Chen","doi":"10.1016/j.stemcr.2025.102397","DOIUrl":"10.1016/j.stemcr.2025.102397","url":null,"abstract":"MEK (mitogen-activated protein kinase) inhibitor is widely used for culturing pluripotent stem cells, while prolonged MEK inhibition compromises the developmental potential of mouse embryonic stem cells (ESCs), implying a dual role of MEK/ERK (extracellular signal-regulated kinase) signaling in pluripotency maintenance. To better understand the mechanism of MEK/ERK in pluripotency maintenance, we performed quantitative phosphoproteomic analysis and identified 169 ERK substrates, which are enriched for proteins involved in stem cell population maintenance, embryonic development, and mitotic cell cycle. Next, we demonstrated that ERK phosphorylates a well-known pluripotency factor ESRRB on Serine 42 and 43. Dephosphorylation of ESRRB facilitates its binding to pluripotency genes, thus enhancing its activity to maintain pluripotency. In contrast, phosphorylation of ESRRB increases its binding to extraembryonic endoderm (XEN) genes, consequently promoting XEN differentiation of ESCs. Altogether, our study reveals that ERK may regulate ESC self-renewal and differentiation by phosphorylating multiple substrates, including ESRRB, which affects both ESC self-renewal and XEN differentiation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102397"},"PeriodicalIF":5.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370912","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

Cardiac differentiation roadmap for analysis of plasticity and balanced lineage commitment. 心脏分化路线图分析可塑性和平衡谱系承诺。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-11 Epub Date: 2025-02-27 DOI: 10.1016/j.stemcr.2025.102422

Rebecca R Snabel, Carla Cofiño-Fabrés, Marijke Baltissen, Verena Schwach, Robert Passier, Gert Jan C Veenstra

{"title":"Cardiac differentiation roadmap for analysis of plasticity and balanced lineage commitment.","authors":"Rebecca R Snabel, Carla Cofiño-Fabrés, Marijke Baltissen, Verena Schwach, Robert Passier, Gert Jan C Veenstra","doi":"10.1016/j.stemcr.2025.102422","DOIUrl":"10.1016/j.stemcr.2025.102422","url":null,"abstract":"Stem cell-based models of human heart tissue and cardiac differentiation employ monolayer and 3D organoid cultures with different properties, cell type composition, and maturity. Here we show how cardiac monolayer, embryoid body, and engineered heart tissue trajectories compare in a single-cell roadmap of atrial and ventricular differentiation conditions. Using a multiomic approach and gene-regulatory network inference, we identified regulators of the epicardial, atrial, and ventricular cardiomyocyte lineages. We identified ZNF711 as a regulatory switch and safeguard for cardiomyocyte commitment. We show that ZNF711 ablation prevents cardiomyocyte differentiation in the absence of retinoic acid, causing progenitors to be diverted more prominently to epicardial and other lineages. Retinoic acid rescues this shift in lineage commitment and promotes atrial cardiomyocyte differentiation by regulation of shared and complementary target genes, showing interplay between ZNF711 and retinoic acid in cardiac lineage commitment.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102422"},"PeriodicalIF":5.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531794","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