Stem Cell Reports最新文献

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-28 DOI: 10.1016/j.stemcr.2025.102478

Jacob A Klickstein, Michelle A Johnson, Pantelis Antonoudiou, Jamie Maguire, Joao A Paulo, Steve P Gygi, Chris Weihl, Malavika Raman

引用次数: 0

Competing dynamic gene regulatory networks involved in fibroblast reprogramming to hematopoietic progenitor cells. 参与成纤维细胞重编程为造血祖细胞的竞争动态基因调控网络。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-25 DOI: 10.1016/j.stemcr.2025.102473

Samiyah Shafiq, Kiyofumi Hamashima, Laura A Guest, Ali H Al-Anbaki, Fabio M R Amaral, Daniel H Wiseman, Valerie Kouskoff, Georges Lacaud, Yuin-Han Loh, Kiran Batta

{"title":"Competing dynamic gene regulatory networks involved in fibroblast reprogramming to hematopoietic progenitor cells.","authors":"Samiyah Shafiq, Kiyofumi Hamashima, Laura A Guest, Ali H Al-Anbaki, Fabio M R Amaral, Daniel H Wiseman, Valerie Kouskoff, Georges Lacaud, Yuin-Han Loh, Kiran Batta","doi":"10.1016/j.stemcr.2025.102473","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102473","url":null,"abstract":"Direct reprogramming of somatic cells offers a potentially safer therapeutic approach to generate patient-specific hematopoietic cells. However, this strategy is limited by stochasticity of reprogramming. Investigating the gene regulatory networks involved during reprogramming would help generate functional cells in adequate numbers. To address this, we developed an inducible system to reprogram fibroblasts to hematopoietic progenitor cells by ectopically expressing the two transcription factors SCL and LMO2. Transcriptome and epigenome analysis at different stages of reprogramming revealed uniform silencing of fibroblast genes and upregulation of the hemogenic endothelial program. Integrated analysis suggested that the transcription factors FLI1, GATA1/2, and KLF14 are direct targets of SCL/LMO2, which subsequently induce the hematopoietic program. Single-cell RNA sequencing revealed conflicting and competing fate decisions at intermediate stages of reprogramming. Inhibiting signaling pathways associated with competing neuronal fate enhanced reprogramming efficiency. In conclusion, this study identifies early/intermediate reprogramming events and associated pathways that could be targeted to improve reprogramming efficiency.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102473"},"PeriodicalIF":5.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gene reactivation upon erosion of X chromosome inactivation in female hiPSCs is predictable yet variable and persists through differentiation. 在女性hiPSCs中，X染色体失活后的基因再激活是可预测的，但也是可变的，并通过分化持续存在。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-25 DOI: 10.1016/j.stemcr.2025.102472

Ana Cláudia Raposo, Paulo Caldas, Joana Jeremias, Maria Arez, Francisca Cazaux Mateus, Pedro Barbosa, Rui Sousa-Luís, Frederico Água, David Oxley, Annalisa Mupo, Melanie Eckersley-Maslin, Miguel Casanova, Ana Rita Grosso, Simão Teixeira da Rocha

{"title":"Gene reactivation upon erosion of X chromosome inactivation in female hiPSCs is predictable yet variable and persists through differentiation.","authors":"Ana Cláudia Raposo, Paulo Caldas, Joana Jeremias, Maria Arez, Francisca Cazaux Mateus, Pedro Barbosa, Rui Sousa-Luís, Frederico Água, David Oxley, Annalisa Mupo, Melanie Eckersley-Maslin, Miguel Casanova, Ana Rita Grosso, Simão Teixeira da Rocha","doi":"10.1016/j.stemcr.2025.102472","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102472","url":null,"abstract":"Female human induced pluripotent stem cells frequently undergo X-chromosome inactivation (XCI) erosion, marked by X-inactive specific transcript (XIST) RNA loss and partial reactivation of the inactive X (Xi). This overlooked phenomenon limits our understanding of its impact on stem cell applications. Here, we show that XCI erosion is frequent and heterogeneous, leading to the reactivation of several X-linked genes. These are primarily located on the short arm of the X chromosome, particularly near escape genes and within H3K27me3-enriched domains, with reactivation linked to reduced promoter DNA methylation. Interestingly, escape genes further increase their expression from Xi upon XCI erosion, highlighting the critical role of XIST in their dosage regulation. Importantly, global (hydroxy)methylation levels and imprinted regions remain unaffected, and analysis of trilineage commitment and cardiomyocyte formation reveals that XCI erosion persists across differentiation. These findings underscore the need for greater awareness of the implications of XCI erosion for stem cell research and clinical applications.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102472"},"PeriodicalIF":5.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Large-scale analysis of loss of chromosome Y in human pluripotent stem cells: Implications for Turner syndrome and ribosomopathies. 人类多能干细胞Y染色体缺失的大规模分析：对特纳综合征和核糖体病的影响。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-24 DOI: 10.1016/j.stemcr.2025.102471

Roni Sarel-Gallily, Keith M Gunapala, Nissim Benvenisty

引用次数: 0

Human cone photoreceptor transplantation stimulates remodeling and restores function in AIPL1 model of end-stage Leber congenital amaurosis. 人锥体光感受器移植刺激终末期Leber先天性黑朦AIPL1模型的重塑和功能恢复。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-18 DOI: 10.1016/j.stemcr.2025.102470

Christopher A Procyk, Anna Melati, Joana Ribeiro, Jingshu Liu, Matthew J Branch, Jamie D Delicata, Menahil Tariq, Aikaterini A Kalarygrou, Jessica Kapadia, Majid Moshtagh Khorsani, Emma L West, Alexander J Smith, Anai Gonzalez-Cordero, Robin R Ali, Rachael A Pearson

{"title":"Human cone photoreceptor transplantation stimulates remodeling and restores function in AIPL1 model of end-stage Leber congenital amaurosis.","authors":"Christopher A Procyk, Anna Melati, Joana Ribeiro, Jingshu Liu, Matthew J Branch, Jamie D Delicata, Menahil Tariq, Aikaterini A Kalarygrou, Jessica Kapadia, Majid Moshtagh Khorsani, Emma L West, Alexander J Smith, Anai Gonzalez-Cordero, Robin R Ali, Rachael A Pearson","doi":"10.1016/j.stemcr.2025.102470","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102470","url":null,"abstract":"Photoreceptor degeneration is a leading cause of untreatable sight loss. Previously, we showed that human pluripotent stem cell-derived cone photoreceptors (hCones) can rescue retinal function in the Rd1 mouse model of rod-cone dystrophy. However, retinal degenerations display markedly different severities and concomitant remodeling of the remaining retina; for photoreceptor replacement therapy to be broadly effective, it must work for a variety of disease phenotypes. Here, we sought to rescue the Aipl1-/- model of Leber congenital amaurosis, a particularly fast, severe condition. After transplantation of hCones, host cone bipolar cells underwent extensive remodeling and formed nascent synaptic-like connections. Electrophysiological recordings showed robust rescue of light-evoked activity across visually relevant photopic intensities, and treated mice exhibited visually evoked optokinetic head-tracking behavior. Thus, human cone photoreceptor replacement therapy is feasible even in very severe cases of retinal dystrophy, offering promise as a disease-agnostic therapy in Leber congenital amaurosis (LCA) and in other advanced retinal degenerations.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102470"},"PeriodicalIF":5.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differentiation success of reprogrammed cells is heterogeneous in vivo and modulated by somatic cell identity memory. 重编程细胞的分化成功在体内是异质性的，并受体细胞身份记忆的调节。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-12 DOI: 10.1016/j.stemcr.2025.102447

Tomas Zikmund, Jonathan Fiorentino, Chris Penfold, Marco Stock, Polina Shpudeiko, Gaurav Agarwal, Larissa Langfeld, Kseniya Petrova, Leonid Peshkin, Stephan Hamperl, Antonio Scialdone, Eva Hoermanseder

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 5.9 2区医学

Stem Cell Reports Pub Date : 2025-03-12 DOI: 10.1016/j.stemcr.2025.102452

Stefania Apostolou, Vanessa Donega

引用次数: 0

Safe CNV removal is crucial for successful hESC-RPE transplantation in wet age-related macular degeneration. 安全的CNV去除是湿性年龄相关性黄斑变性患者hESC-RPE移植成功的关键。

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.2025.102424

Ying Xue Lv, Qi You Li, Ping Duan, Min Fang Zhang, Bo Liu, Shi Ying Li, Tong Tao Zhao, Hao Wang, Yong Liu, Zheng Qin Yin

{"title":"Safe CNV removal is crucial for successful hESC-RPE transplantation in wet age-related macular degeneration.","authors":"Ying Xue Lv, Qi You Li, Ping Duan, Min Fang Zhang, Bo Liu, Shi Ying Li, Tong Tao Zhao, Hao Wang, Yong Liu, Zheng Qin Yin","doi":"10.1016/j.stemcr.2025.102424","DOIUrl":"10.1016/j.stemcr.2025.102424","url":null,"abstract":"Subretinal transplantation of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells has demonstrated therapeutic potential in macular degeneration. However, its efficiency is limited in wet age-related macular degeneration (wet AMD) due to choroidal neovascularization (CNV). To investigate the feasibility of hESC-RPE cell transplantation, we employed a surgical approach to induce retinal detachment, which allowed the removal of CNV lesions. After retinal reattachment, hESC-RPE cells were transplanted into the subretinal space. Ten patients were enrolled and divided into 2 groups. No retinal edema or CNV recurrence was observed in group 1 (7 patients without bleeding). Group 2 (3 patients with bleeding) had persistent fundus inflammation, and one patient experienced CNV recurrence. All patients were managed effectively without vision loss. These findings suggest that subretinal transplantation of hESC-RPE cells after CNV removal is safe and well tolerated; however, damage caused during CNV removal may trigger persistent inflammation and CNV recurrence. This study was registered at ClinicalTrials.gov (NCT02749734).","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102424"},"PeriodicalIF":5.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531796","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

Response to Yu et al. 对Yu等人的回应。

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.2025.102400

Yuanyue Liu, Siqi Song, Youyu Liu, Ting Fu, Yanzheng Guo, Ruoqing Liu, Jiexing Chen, Yanchun Lin, Yaqi Cheng, Yun Li, Tian Guan, Shiqi Ling, Haoyu Zeng

引用次数: 0

20 years of stemness: From stem cells to hypertranscription and back. 20年的干细胞：从干细胞到超转录再回来。

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.2025.102406

Yun-Kyo Kim, Miguel Ramalho-Santos

引用次数: 0