Stem Cell ReportsPub Date : 2025-07-04DOI: 10.1016/j.stemcr.2025.102577
Kaoru Takasaki, Eric K Wafula, Jian Meng Fan, Ying Ting Sit, Sara S Kumar, David Smith, Alyssa Gagne, Peter A Gearhart, Deborah L French, Christopher S Thom, Stella T Chou
{"title":"Single-cell transcriptomics reveal individual and cooperative effects of trisomy 21 and GATA1s on hematopoiesis.","authors":"Kaoru Takasaki, Eric K Wafula, Jian Meng Fan, Ying Ting Sit, Sara S Kumar, David Smith, Alyssa Gagne, Peter A Gearhart, Deborah L French, Christopher S Thom, Stella T Chou","doi":"10.1016/j.stemcr.2025.102577","DOIUrl":"10.1016/j.stemcr.2025.102577","url":null,"abstract":"<p><p>Trisomy 21 (T21) is associated with baseline erythrocytosis, thrombocytopenia, neutrophilia, transient abnormal myelopoiesis (TAM), and myeloid leukemia of Down syndrome (ML-DS). TAM and ML-DS blasts harbor mutations in GATA1, resulting in the exclusive expression of the truncated isoform GATA1s. Germline GATA1s mutations in individuals without T21 cause congenital cytopenias, typically without a leukemic predisposition. To dissect the developmental effects of T21 and GATA1s, we used a combination of isogenic human induced pluripotent stem cells, primary human fetal and neonatal cells, and single-cell transcriptomics to interrogate hematopoietic progenitors differing only by chromosome 21 and/or GATA1 status. Both T21 and GATA1s induced early lineage skewing, and trajectory analysis revealed that GATA1s altered the temporal regulation of lineage-specific transcriptional programs, disrupting cell proliferation and maturation irrespective of chromosomal context. These studies uncovered unexpected heterogeneity and lineage priming in early, multipotent hematopoietic progenitors and identified transcriptional and functional maturation blocks linked to GATA1s.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102577"},"PeriodicalIF":5.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668550","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}
Stem Cell ReportsPub Date : 2025-07-03DOI: 10.1016/j.stemcr.2025.102575
Sriivatsan G Rajan, Lynne M Nacke, Joseph N Lombardo, Farid Manuchehrfar, Kaelan Wong, Pinal Kanabar, Elizabeth A Somodji, Jocelyn Garcia, Mark Maienschein-Cline, Jie Liang, Ankur Saxena
{"title":"Progenitor neighborhoods function as transient niches to sustain olfactory neurogenesis.","authors":"Sriivatsan G Rajan, Lynne M Nacke, Joseph N Lombardo, Farid Manuchehrfar, Kaelan Wong, Pinal Kanabar, Elizabeth A Somodji, Jocelyn Garcia, Mark Maienschein-Cline, Jie Liang, Ankur Saxena","doi":"10.1016/j.stemcr.2025.102575","DOIUrl":"10.1016/j.stemcr.2025.102575","url":null,"abstract":"<p><p>Olfactory neurogenesis occurs throughout the lives of vertebrates, including in humans, and relies on the continuous differentiation and integration of neurons into a complex network. How progenitor cells convert fluctuations in cell-cell signaling into streamlined fate decisions over both space and time is poorly understood. Here, we track multicellular dynamics in the zebrafish olfactory epithelium, undertake targeted perturbations, and find that neurogenesis is driven by mutual antagonism between Notch signaling and insulinoma-associated 1a (Insm1a) that is responsive to inter-organ retinoic acid signaling. Single-cell analysis reveals that olfactory neurons emerge from transient groups of cells termed cellular neighborhoods. Stochastic modeling shows that neighborhood self-assembly is maintained by a tightly regulated bistable toggle switch. Differentiating cells migrate apically in response to brain-derived neurotrophic factor (BDNF) to take up residence as mature sensory neurons. Cumulatively, these findings reveal how stochastic signaling networks spatiotemporally regulate a balance between progenitors and derivatives, driving sustained neurogenesis in an intricate organ system.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102575"},"PeriodicalIF":5.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565316","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}
Stem Cell ReportsPub Date : 2025-06-28DOI: 10.1016/j.stemcr.2025.102574
Georgia Lokka, Anna Chantzara, Zoi Lygerou, Stavros Taraviras
{"title":"Ependymal and neural stem cells are close relatives.","authors":"Georgia Lokka, Anna Chantzara, Zoi Lygerou, Stavros Taraviras","doi":"10.1016/j.stemcr.2025.102574","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102574","url":null,"abstract":"<p><p>Multiciliated ependymal and neural stem cells are key cell populations of the subventricular zone. Recent findings revealed that at least a subpopulation of radial glial cells during embryogenesis can be bipotent and produce both neural stem cells and ependymal cells. The balance between these cell populations is orchestrated by Geminin superfamily, ensuring optimal niche function. However, whether cell fate decisions are definitive or dynamic and whether potential regional differences exist remain elusive. In this review, we delve into the shared origins of different subventricular zone cell populations, and we explore the potential interplay among them. Moreover, we compile evidence on the de-differentiation capacity of ependymal cells and their controversial neural stem cell function under specific conditions, with emphasis on the possible implication of a rare population of biciliated (E2) ependymal cells. Understanding the mechanisms regulating cell fate decisions may unravel ependymal cells' therapeutic potential in therapies targeting various human diseases.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102574"},"PeriodicalIF":5.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565248","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}
Stem Cell ReportsPub Date : 2025-06-25DOI: 10.1016/j.stemcr.2025.102572
Sophie E Givens, Abygail A Andebrhan, Ruchen Wang, Xiangzhen Kong, Taylor M Rothermel, Sanaz Hosseini, An Xie, Mohammad Shameem, Andrea A Torniainen, Somayeh Ebrahimi-Barough, Samuel F Boland, Maya Johnson, Natalia Calixto Mancipe, Bhairab N Singh, Samuel Dudley, Patrick W Alford, Elena G Tolkacheva, Jop H van Berlo, Brenda M Ogle
{"title":"Developmental cues from epicardial cells simultaneously promote cardiomyocyte proliferation and electrochemical maturation.","authors":"Sophie E Givens, Abygail A Andebrhan, Ruchen Wang, Xiangzhen Kong, Taylor M Rothermel, Sanaz Hosseini, An Xie, Mohammad Shameem, Andrea A Torniainen, Somayeh Ebrahimi-Barough, Samuel F Boland, Maya Johnson, Natalia Calixto Mancipe, Bhairab N Singh, Samuel Dudley, Patrick W Alford, Elena G Tolkacheva, Jop H van Berlo, Brenda M Ogle","doi":"10.1016/j.stemcr.2025.102572","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102572","url":null,"abstract":"<p><p>Accumulating evidence indicates that maturation limits cardiomyocyte proliferation. We expand on that theory by co-culturing human induced pluripotent stem cell (hiPSC)-cardiomyocytes (CM) with epicardial cells (EPCs) and epicardial-derived cells in both 2D co-cultures and 3D engineered heart tissues (EHTs). In 2D co-cultures, the percentage of proliferating CM increased in parallel with stark electrophysiologic improvements. Single-cell transcriptomics revealed a significant shift in the bulk CM population of the epicardial-CM co-cultures as characterized by more fetal-like myofilament isoforms but with enhanced pathways associated with electrochemical maturation. The 3D-EHTs containing EPCs showed more limited proliferation but a similar improvement in CM electrophysiologic function. Next, epicardial-derived fibroblasts (EPD-FBs) were added to the EHTs containing EPCs, and we observed significant myofilament maturation and increased force generation. Our results suggest that some aspects of CM maturation (i.e., electrochemical) can occur when proliferation rates are relatively high, and that sarcomere-associated mechanical maturation occurs at later developmental stages when proliferation has largely ceased.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102572"},"PeriodicalIF":5.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565246","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}
Stem Cell ReportsPub Date : 2025-06-25DOI: 10.1016/j.stemcr.2025.102571
Yang Jo Chung, Ryan Bertoli, Dengchao Cao, Robert L Walker, Yuelin Jack Zhu, Paul Meltzer, Peter D Aplan
{"title":"Disruption of normal stem cell function and transmission of myelodysplastic syndrome by self-renewal of committed myeloid lineage cells.","authors":"Yang Jo Chung, Ryan Bertoli, Dengchao Cao, Robert L Walker, Yuelin Jack Zhu, Paul Meltzer, Peter D Aplan","doi":"10.1016/j.stemcr.2025.102571","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102571","url":null,"abstract":"<p><p>The ineffective hematopoiesis of myelodysplastic syndrome (MDS) suggests that hematopoietic stem and progenitor cells (HSPCs) are defective. Here, we demonstrate that NUP98::HOXD13 (NHD13) MDS mice have significantly decreased functional HSPCs. Moreover, in contrast to wild-type (WT) bone marrow (BM), lineage-positive (Lin<sup>+</sup>) BM cells from NHD13 mice have self-renewal potential. Specific subsets of NHD13 Lin<sup>+</sup> cells that express B220 and Kit antigens were able to self-renew and generate MDS in WT recipients. Although this unique B220<sup>+</sup>Kit<sup>+</sup> phenotype could be found in WT as well as NHD13 BM, the population was markedly increased in NHD13 BM. Further characterization using Mac1 and Gr1 markers revealed that both Mac1<sup>+</sup>Gr1<sup>+</sup>B220<sup>+</sup>Kit<sup>+</sup> and Mac1<sup>-</sup>Gr1<sup>-</sup> B220<sup>+</sup>Kit<sup>+</sup> populations showed self-renewal and led to an MDS phenotype in WT recipients. Taken together, these findings demonstrate that as normal hematopoiesis derived from typical HSPCs decreases in NHD13 mice, committed hematopoietic progenitor cells proliferate, self-renew, and initiate MDS.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102571"},"PeriodicalIF":5.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565247","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}
Stem Cell ReportsPub Date : 2025-06-24DOI: 10.1016/j.stemcr.2025.102576
Colin Trepicchio, Gat Rauner, Nicole Traugh, Ruohong Wang, Meadow Parrish, Daniel E C Fein, Youssof Mal, Piyush B Gupta, Stefano Monti, Charlotte Kuperwasser
{"title":"DDR1 regulates RUNX1-CBFβ to control breast stem cell differentiation.","authors":"Colin Trepicchio, Gat Rauner, Nicole Traugh, Ruohong Wang, Meadow Parrish, Daniel E C Fein, Youssof Mal, Piyush B Gupta, Stefano Monti, Charlotte Kuperwasser","doi":"10.1016/j.stemcr.2025.102576","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102576","url":null,"abstract":"<p><p>Understanding epithelial stem cell differentiation and morphogenesis during breast tissue development is essential, as disruption in these processes underlie breast cancer formation. We used a next-generation single-cell-derived organoid model to investigate how individual stem cells give rise to complex tissue. We show that discoidin domain receptor 1 (DDR1) inhibition traps cells in a bipotent state, blocking alveolar morphogenesis and luminal cell expansion, which is necessary for complex epithelium formation. Disrupting RUNX1 function produced nearly identical phenotypes, underscoring its critical role downstream of DDR1. Mechanistically, DDR1 affects the interaction and expression of RUNX1 and its cofactor core binding factor beta (CBFβ), thereby regulating its activity. Mutational analyses in breast cancer patients reveal frequent alterations in the DDR1-RUNX1 signaling axis, particularly co-occurring mutations. Together, these findings uncover DDR1-RUNX1 as a central signaling pathway driving breast epithelial differentiation, whose dysregulation may contribute fundamentally to breast cancer pathogenesis.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102576"},"PeriodicalIF":5.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565245","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}
Stem Cell ReportsPub Date : 2025-06-21DOI: 10.1016/j.stemcr.2025.102570
Emily Maguire, Jincy Winston, Sarah H Ellwood, Rachel O'Donoghue, Bethany Shaw, Atahualpa Castillo Morales, Samuel Keat, Alexandra Evans, Rachel Marshall, Lauren Luckcuck, Laura Brown, Elisa Salis, Ganna Leonenko, Nicola Denning, Nicholas D Allen, Valentina Escott-Price, Caleb Webber, Philip R Taylor, Rebecca Sims, Sally A Cowley, Julie Williams, Sarah M Carpanini, Hazel Hall-Roberts
{"title":"Modeling common Alzheimer's disease with high and low polygenic risk in human iPSC: A large-scale research resource.","authors":"Emily Maguire, Jincy Winston, Sarah H Ellwood, Rachel O'Donoghue, Bethany Shaw, Atahualpa Castillo Morales, Samuel Keat, Alexandra Evans, Rachel Marshall, Lauren Luckcuck, Laura Brown, Elisa Salis, Ganna Leonenko, Nicola Denning, Nicholas D Allen, Valentina Escott-Price, Caleb Webber, Philip R Taylor, Rebecca Sims, Sally A Cowley, Julie Williams, Sarah M Carpanini, Hazel Hall-Roberts","doi":"10.1016/j.stemcr.2025.102570","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102570","url":null,"abstract":"<p><p>Common forms of Alzheimer's disease (AD) are complex and polygenic. We have created a research resource that seeks to capture the extremes of polygenic risk in a collection of human induced pluripotent stem cell (iPSC) lines from over 100 donors: the IPMAR Resource (iPSC Platform to Model Alzheimer's Disease Risk). Donors were selected from a large UK cohort of 6,000+ research-diagnosed early or late-onset AD cases and elderly cognitively healthy controls, many of whom have lived through the age of risk for disease development (>85 years). We include iPSC with extremes of global AD polygenic risk (high-risk late-onset AD: 34; high-risk early-onset AD: 29; low-risk control: 27) as well as those reflecting complement pathway-specific genetic risk (high-risk AD: 9; low-risk controls: 10). All iPSC have associated clinical, longitudinal, and genetic datasets and will be available through collaboration or from cell (EBiSC) and data (DPUK) repositories.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102570"},"PeriodicalIF":5.9,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565249","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}
Stem Cell ReportsPub Date : 2025-06-19DOI: 10.1016/j.stemcr.2025.102546
Betty Cohn, Megan Doerr, Pamela Feliciano, Stephanie M Fullerton, Saskia Hendriks, Soren Holm, Insoo Hyun, Karin Jongsma, Karen M Meagher, M Elizabeth Ross, Jason L Stein, Sharon F Terry, Katherine E MacDuffie
{"title":"Transparency and ongoing communication with participants in brain organoid research: Consensus of an interdisciplinary working group.","authors":"Betty Cohn, Megan Doerr, Pamela Feliciano, Stephanie M Fullerton, Saskia Hendriks, Soren Holm, Insoo Hyun, Karin Jongsma, Karen M Meagher, M Elizabeth Ross, Jason L Stein, Sharon F Terry, Katherine E MacDuffie","doi":"10.1016/j.stemcr.2025.102546","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102546","url":null,"abstract":"<p><p>Stem cell-based models of the human brain benefit from biospecimens that can be used for a broad range of future research. But current regulations do not address the desire of research participants to remain engaged beyond initial biospecimen donation. We present practicable strategies for engaging participants while preserving scientific potential.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102546"},"PeriodicalIF":5.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512529","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}
{"title":"Two types of regenerative cell populations appear in acute liver injury.","authors":"Tomomi Aoyagi, Takeshi Goya, Koji Imoto, Yuki Azuma, Tomonobu Hioki, Motoyuki Kohjima, Masatake Tanaka, Yoshinao Oda, Yoshihiro Ogawa","doi":"10.1016/j.stemcr.2025.102503","DOIUrl":"10.1016/j.stemcr.2025.102503","url":null,"abstract":"<p><p>The liver has a robust regenerative capacity. However, the mechanisms underlying this process remain unclear. Numerous studies on liver regeneration have been previously conducted using partial hepatectomy models, which may not fully represent acute liver injury with inflammation and necrosis. This is commonly observed in the majority of clinical cases. In this study, we conducted a single-cell RNA sequencing (RNA-seq) analysis of liver regeneration in acetaminophen-treated mice using publicly available data. We found that two distinct populations of regenerative cells simultaneously appeared within the same regenerative process. The two populations significantly differed in terms of cell morphology, differentiation, localization, proliferation rate, and signal response. Moreover, one of the populations was induced by contact with necrotic tissue and demonstrated a higher proliferative capacity with a dedifferentiated feature. These findings provide new insights into liver regeneration and therapeutic strategies for liver failure.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102503"},"PeriodicalIF":5.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023686","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
