Stem Cell ReportsPub Date : 2025-06-10Epub Date: 2025-05-22DOI: 10.1016/j.stemcr.2025.102508
Brian W Basinski, Yuanhao Huang, Qiang Li, Charukesi D Sivakumar, Tyler J Carman, Hana M Pan, Jing Xu, D Ford Hannum, Jie Liu, Rajesh C Rao
{"title":"A zinc finger-dependent, PRDM13-driven mechanism regulates retinal progenitor cell fate from mouse embryonic stem cells via WNT signaling.","authors":"Brian W Basinski, Yuanhao Huang, Qiang Li, Charukesi D Sivakumar, Tyler J Carman, Hana M Pan, Jing Xu, D Ford Hannum, Jie Liu, Rajesh C Rao","doi":"10.1016/j.stemcr.2025.102508","DOIUrl":"10.1016/j.stemcr.2025.102508","url":null,"abstract":"<p><p>The transcriptional regulation underlying eye field (retinal primordium) development requires precise control, yet the mechanisms guiding lineage-specific differentiation within the central nervous system (CNS) remain incompletely understood. Using neuroectoderm (NE) organoids derived from mouse embryonic stem cells, we investigate the role of PRDM13 in eye field specification. We demonstrate that Prdm13 expression inhibits RX<sup>+</sup> eye field fate but permits non-eye field NE differentiation, an effect that depends on its first and second zinc-finger domains. Prdm13 activates the WNT/β-catenin signaling pathway during differentiation, leading to downregulation of key transcription factors crucial for establishing the eye field. Pharmacological inhibition of WNT signaling abolishes PRDM13-mediated suppression, restoring RX<sup>+</sup> eye field differentiation. Our work reveals a previously undescribed PRDM13-WNT signaling axis that regulates lineage-specific neural differentiation of embryonic stem cells.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102508"},"PeriodicalIF":5.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133290","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}
Stem Cell ReportsPub Date : 2025-06-05DOI: 10.1016/j.stemcr.2025.102533
Marloes Verkerke, Maarten H Werkman, Vanessa Donega
{"title":"Neural stem cells of the subventricular zone: A potential stem cell pool for brain repair in Parkinson's disease.","authors":"Marloes Verkerke, Maarten H Werkman, Vanessa Donega","doi":"10.1016/j.stemcr.2025.102533","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102533","url":null,"abstract":"<p><p>Parkinson's disease is a neurodegenerative disease caused by the degeneration of dopaminergic neurons in the substantia nigra. There are no curative treatments, and therefore, there is an urgent need for new approaches. One potential strategy being investigated is stem cell-based approaches to replace lost neurons, by, for example, harnessing endogenous neural stem cells (NSCs). These cells are found in the subventricular zone (SVZ) aligning the lateral ventricles and remain in a dormant state in the aged and diseased mammalian brain. However, with the appropriate stimuli, NSCs can shift into an activated state, proliferate, and differentiate. In this review, we discuss how PD pathology affects the behavior of NSCs and current pharmacological strategies to boost regeneration in PD. NSCs of the SVZ could be a stem cell source for brain repair, and future studies should shed light on whether these stem cells have the potential to produce functional neuronal cells.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102533"},"PeriodicalIF":5.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294939","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 : 2025-05-13Epub Date: 2025-04-24DOI: 10.1016/j.stemcr.2025.102481
Jessica K Cinkornpumin, Sin Young Kwon, Anna-Maria Prandstetter, Theresa Maxian, Jacinthe Sirois, James Goldberg, Joy Zhang, Deepak Saini, Purbasa Dasgupta, Mariyan J Jeyarajah, Stephen J Renaud, Soumen Paul, Sandra Haider, William A Pastor
{"title":"Hypoxia and loss of GCM1 expression prevent differentiation and contact inhibition in human trophoblast stem cells.","authors":"Jessica K Cinkornpumin, Sin Young Kwon, Anna-Maria Prandstetter, Theresa Maxian, Jacinthe Sirois, James Goldberg, Joy Zhang, Deepak Saini, Purbasa Dasgupta, Mariyan J Jeyarajah, Stephen J Renaud, Soumen Paul, Sandra Haider, William A Pastor","doi":"10.1016/j.stemcr.2025.102481","DOIUrl":"10.1016/j.stemcr.2025.102481","url":null,"abstract":"<p><p>During the first stages of embryonic development, the placenta develops under very low oxygen tension (∼1%-2% O<sub>2</sub>), so we sought to determine the regulatory role of oxygen in human trophoblast stem cells (hTSCs). We find that low oxygen promotes hTSC self-renewal but inhibits differentiation to syncytiotrophoblast (STB) and extravillous trophoblast (EVT). The transcription factor GCM1 (glial cell missing transcription factor 1) is downregulated in low oxygen, and concordantly, there is substantial reduction of GCM1-regulated genes in hypoxic conditions. Knockout of GCM1 in hTSC likewise impaired EVT and STB formation. Treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor reported to reduce GCM1 protein levels likewise counteracts spontaneous or directed differentiation. Additionally, chromatin immunoprecipitation of GCM1 showed binding near key genes upregulated upon differentiation including the contact inhibition factor CDKN1C. Loss of GCM1 resulted in downregulation of CDKN1C and corresponding loss of contact inhibition, implicating GCM1 in regulation of this critical process.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102481"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044611","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}
Stem Cell ReportsPub Date : 2025-05-13Epub Date: 2025-04-03DOI: 10.1016/j.stemcr.2025.102471
Roni Sarel-Gallily, Keith M Gunapala, Nissim Benvenisty
{"title":"Large-scale analysis of loss of chromosome Y in human pluripotent stem cells: Implications for Turner syndrome and ribosomopathies.","authors":"Roni Sarel-Gallily, Keith M Gunapala, Nissim Benvenisty","doi":"10.1016/j.stemcr.2025.102471","DOIUrl":"10.1016/j.stemcr.2025.102471","url":null,"abstract":"<p><p>Loss of chromosome Y (LOY) occurs in aging and cancers, but its extent and implications in human embryonic stem cells (hESCs) have not been studied. Here, we analyzed over 2,650 RNA sequencing (RNA-seq) samples from hESCs and their differentiated derivatives to detect LOY. We found that 12% of hESC samples have lost their chromosome Y and identified LOY in all three germ layers. Differential expression analysis revealed that LOY samples showed a decrease in expression of pluripotency markers and in ribosomal protein (RP) genes. Strikingly, significant RP transcription downregulation was observed in most RP genes, although there is only one expressed Y-linked RP gene. We further analyzed RP expression in Turner syndrome and Diamond-Blackfan anemia samples and observed overall downregulation of RP transcription. This broad analysis sheds light on the scope and effects of LOY in hESCs, suggesting a novel dosage-sensitive mechanism regulating RP gene transcription in LOY and autosomal ribosomopathies.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102471"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789028","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}
Stem Cell ReportsPub Date : 2025-05-13Epub Date: 2025-05-01DOI: 10.1016/j.stemcr.2025.102498
Matilda Beckett, Sarah Franklin, Peter J Rugg-Gunn
{"title":"Identifying enabling strategies for effective public dialogue in human embryo research.","authors":"Matilda Beckett, Sarah Franklin, Peter J Rugg-Gunn","doi":"10.1016/j.stemcr.2025.102498","DOIUrl":"10.1016/j.stemcr.2025.102498","url":null,"abstract":"<p><p>Public dialogue is crucial for understanding societal views on human embryo research, and the complexity and sensitivity of this topic require special considerations of how such dialogues are facilitated. Here, we identify enablers of effective dialogue, which can improve the design and delivery of engagement exercises related to embryo research.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102498"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039122","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}
{"title":"CD37 regulates the self-renewal of leukemic stem cells via integrin-mediated signaling in acute myeloid leukemia.","authors":"Jinyuan Lu, Lixin Lv, Xiaoxue Tian, Zheng Li, Yuting Ma, Nannan Li, Jian Wang, Guangming Wang, Yu Zeng, Wenjun Zhang, Jun Xu, Aibin Liang","doi":"10.1016/j.stemcr.2025.102476","DOIUrl":"10.1016/j.stemcr.2025.102476","url":null,"abstract":"<p><p>Leukemic stem cells (LSCs) are a small subset of leukemia cells that drive leukemia initiation and maintenance. Herein, we report that CD37, a member of transmembrane 4 superfamily (TM4SF), regulates the survival of acute myeloid leukemia (AML) cells as well as the self-renewal of AML LSCs. The downregulation of CD37 retarded proliferation and increased apoptosis in human AML cell lines THP-1 and OCI-AML2. Deficiency of CD37 in vivo had a minimal effect on normal hematopoiesis but significantly impeded leukemia maintenance and propagation, which led to increased apoptosis and decreased cell cycle entry in AML blasts as well as impaired colony formation and declined frequency of AML LSCs in the serial transplantation. Furthermore, CD37 interacted with integrin α4β7 and activated the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediated by integrin signaling. Our study provides novel insights for targeted therapy of AML, indicating CD37 as a safe and effective target for immunotherapy.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102476"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023668","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}
Stem Cell ReportsPub Date : 2025-05-13Epub Date: 2025-04-03DOI: 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":"10.1016/j.stemcr.2025.102473","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102473"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143154/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2025-05-13Epub Date: 2025-04-24DOI: 10.1016/j.stemcr.2025.102480
Niamh Moriarty, Tyra D Fraser, Cameron P J Hunt, Georgia Eleftheriou, Jessica A Kauhausen, Lachlan H Thompson, Clare L Parish
{"title":"Exercise promotes the functional integration of human stem cell-derived neural grafts in a rodent model of Parkinson's disease.","authors":"Niamh Moriarty, Tyra D Fraser, Cameron P J Hunt, Georgia Eleftheriou, Jessica A Kauhausen, Lachlan H Thompson, Clare L Parish","doi":"10.1016/j.stemcr.2025.102480","DOIUrl":"10.1016/j.stemcr.2025.102480","url":null,"abstract":"<p><p>Human pluripotent stem cell (hPSC)-derived dopamine neurons can functionally integrate and reverse motor symptoms in Parkinson's disease models, motivating current clinical trials. However, dopamine neuron proportions remain low and their plasticity inferior to fetal tissue grafts. Evidence shows exercise can enhance neuron survival and plasticity, warranting investigation for hPSC-derived neural grafts. We show voluntary exercise (wheel running) significantly increases graft plasticity, accelerating motor recovery in animals receiving ectopic, but not homotopic, placed grafts, suggestive of threshold requirements. Plasticity was accompanied by increased phosphorylated extracellular signal-regulated kinase (ERK+) cells in the graft (and host), reflective of mitogen-activated protein kinase (MAPK)-ERK signaling, a downstream target of glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), proteins that were also elevated. Verifying improved graft integration was the increase in cFos+ postsynaptic striatal neurons. These findings have direct implications for the adoption of physical therapy-based approaches to enhance neural transplantation outcomes in future Parkinson's disease clinical trials.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102480"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982182","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}
Stem Cell ReportsPub Date : 2025-05-13Epub Date: 2025-04-24DOI: 10.1016/j.stemcr.2025.102482
Pierre Osteil, Sarah Withey, Nicole Santucci, Nader Aryamanesh, Ignatius Pang, Nazmus Salehin, Jane Sun, Annie Qin, Jiayi Su, Hilary Knowles, Xiucheng Bella Li, Simon Cai, Ernst Wolvetang, Patrick P L Tam
{"title":"MIXL1 activation in endoderm differentiation of human induced pluripotent stem cells.","authors":"Pierre Osteil, Sarah Withey, Nicole Santucci, Nader Aryamanesh, Ignatius Pang, Nazmus Salehin, Jane Sun, Annie Qin, Jiayi Su, Hilary Knowles, Xiucheng Bella Li, Simon Cai, Ernst Wolvetang, Patrick P L Tam","doi":"10.1016/j.stemcr.2025.102482","DOIUrl":"10.1016/j.stemcr.2025.102482","url":null,"abstract":"<p><p>Human induced pluripotent stem cells (hiPSCs) possess the ability to differentiate into a multitude of cell and tissue types but display heterogeneous propensity of differentiation into specific lineage. Characterization of the transcriptome of 11 hiPSC lines showed that activation of MIXL1 at the early stage of stem cell differentiation correlated with higher efficacy in generating definitive endoderm and advancing differentiation and maturation of endoderm derivatives. Enforced expression of MIXL1 in the endoderm-inefficient hiPSCs enhanced the propensity of endoderm differentiation, suggesting that modulation of key drivers of lineage differentiation can re-wire hiPSC to the desired lineage propensity to generate the requisite stem cell products.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102482"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000131","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}
Stem Cell ReportsPub Date : 2025-05-13Epub Date: 2025-04-17DOI: 10.1016/j.stemcr.2025.102477
Hafez Ismaili M'hamdi
{"title":"Language and labels from the lab: Definitions in the stem cell-based embryo model debate.","authors":"Hafez Ismaili M'hamdi","doi":"10.1016/j.stemcr.2025.102477","DOIUrl":"10.1016/j.stemcr.2025.102477","url":null,"abstract":"<p><p>This article examines the definitional challenges surrounding stem cell-based embryo models. Terms like \"synthetic embryos\" misrepresent their nature and influence public discourse. I argue for a multidisciplinary approach, integrating scientific precision with linguistic and ethical considerations, to ensure clarity, honesty, and respect in both scientific and societal debates.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102477"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034783","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}