Stem Cell ReportsPub Date : 2024-05-14Epub Date: 2024-04-04DOI: 10.1016/j.stemcr.2024.03.002
Daniel J Dennis, Beatrix S Wang, Konstantina Karamboulas, David R Kaplan, Freda D Miller
{"title":"Single-cell approaches define two groups of mammalian oligodendrocyte precursor cells and their evolution over developmental time.","authors":"Daniel J Dennis, Beatrix S Wang, Konstantina Karamboulas, David R Kaplan, Freda D Miller","doi":"10.1016/j.stemcr.2024.03.002","DOIUrl":"10.1016/j.stemcr.2024.03.002","url":null,"abstract":"<p><p>Here, we used single-cell RNA sequencing (scRNA-seq), single-cell ATAC sequencing (scATAC-seq), and single-cell spatial transcriptomics to characterize murine cortical OPCs throughout postnatal life. During development, we identified two groups of differentially localized PDGFRα<sup>+</sup> OPCs that are transcriptionally and epigenetically distinct. One group (active, or actOPCs) is metabolically active and enriched in white matter. The second (homeostatic, or hOPCs) is less active, enriched in gray matter, and predicted to derive from actOPCs. In adulthood, these two groups are transcriptionally but not epigenetically distinct, and relative to developing OPCs are less active metabolically and have less open chromatin. When adult oligodendrogenesis is enhanced during experimentally induced remyelination, adult OPCs do not reacquire a developmental open chromatin state, and the oligodendrogenesis trajectory is distinct from that seen neonatally. These data suggest that there are two OPC groups subserving distinct postnatal functions and that neonatal and adult OPC-mediated oligodendrogenesis are fundamentally different.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871955","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 : 2024-05-14Epub Date: 2024-05-02DOI: 10.1016/j.stemcr.2024.04.004
Shoma Nakagawa, Davide Carnevali, Xiangtian Tan, Mariano J Alvarez, David-Emlyn Parfitt, Umberto Di Vicino, Karthik Arumugam, William Shin, Sergi Aranda, Davide Normanno, Ruben Sebastian-Perez, Chiara Cannatá, Paola Cortes, Maria Victoria Neguembor, Michael M Shen, Andrea Califano, Maria Pia Cosma
{"title":"The Wnt-dependent master regulator NKX1-2 controls mouse pre-implantation development.","authors":"Shoma Nakagawa, Davide Carnevali, Xiangtian Tan, Mariano J Alvarez, David-Emlyn Parfitt, Umberto Di Vicino, Karthik Arumugam, William Shin, Sergi Aranda, Davide Normanno, Ruben Sebastian-Perez, Chiara Cannatá, Paola Cortes, Maria Victoria Neguembor, Michael M Shen, Andrea Califano, Maria Pia Cosma","doi":"10.1016/j.stemcr.2024.04.004","DOIUrl":"10.1016/j.stemcr.2024.04.004","url":null,"abstract":"<p><p>Embryo size, specification, and homeostasis are regulated by a complex gene regulatory and signaling network. Here we used gene expression signatures of Wnt-activated mouse embryonic stem cell (mESC) clones to reverse engineer an mESC regulatory network. We identify NKX1-2 as a novel master regulator of preimplantation embryo development. We find that Nkx1-2 inhibition reduces nascent RNA synthesis, downregulates genes controlling ribosome biogenesis, RNA translation, and transport, and induces severe alteration of nucleolus structure, resulting in the exclusion of RNA polymerase I from nucleoli. In turn, NKX1-2 loss of function leads to chromosome missegregation in the 2- to 4-cell embryo stages, severe decrease in blastomere numbers, alterations of tight junctions (TJs), and impairment of microlumen coarsening. Overall, these changes impair the blastocoel expansion-collapse cycle and embryo cavitation, leading to altered lineage specification and developmental arrest.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858043","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 : 2024-05-14Epub Date: 2024-04-04DOI: 10.1016/j.stemcr.2024.03.003
Pavel Tsaytler, Gaby Blaess, Manuela Scholze-Wittler, Frederic Koch, Bernhard G Herrmann
{"title":"Early neural specification of stem cells is mediated by a set of SOX2-dependent neural-associated enhancers.","authors":"Pavel Tsaytler, Gaby Blaess, Manuela Scholze-Wittler, Frederic Koch, Bernhard G Herrmann","doi":"10.1016/j.stemcr.2024.03.003","DOIUrl":"10.1016/j.stemcr.2024.03.003","url":null,"abstract":"<p><p>SOX2 is a transcription factor involved in the regulatory network maintaining the pluripotency of embryonic stem cells in culture as well as in early embryos. In addition, SOX2 plays a pivotal role in neural stem cell formation and neurogenesis. How SOX2 can serve both processes has remained elusive. Here, we identified a set of SOX2-dependent neural-associated enhancers required for neural lineage priming. They form a distinct subgroup (1,898) among 8,531 OCT4/SOX2/NANOG-bound enhancers characterized by enhanced SOX2 binding and chromatin accessibility. Activation of these enhancers is triggered by neural induction of wild-type cells or by default in Smad4-ablated cells resistant to mesoderm induction and is antagonized by mesodermal transcription factors via Sox2 repression. Our data provide mechanistic insight into the transition from the pluripotency state to the early neural fate and into the regulation of early neural versus mesodermal specification in embryonic stem cells and embryos.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860032","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 : 2024-05-14Epub Date: 2024-04-04DOI: 10.1016/j.stemcr.2024.03.004
George Cairns, Madhavee Thumiah-Mootoo, Mah Rukh Abbasi, Melissa Gourlay, Jeremy Racine, Nikita Larionov, Alexandre Prola, Mireille Khacho, Yan Burelle
{"title":"PINK1 deficiency alters muscle stem cell fate decision and muscle regenerative capacity.","authors":"George Cairns, Madhavee Thumiah-Mootoo, Mah Rukh Abbasi, Melissa Gourlay, Jeremy Racine, Nikita Larionov, Alexandre Prola, Mireille Khacho, Yan Burelle","doi":"10.1016/j.stemcr.2024.03.004","DOIUrl":"10.1016/j.stemcr.2024.03.004","url":null,"abstract":"<p><p>Maintenance of mitochondrial function plays a crucial role in the regulation of muscle stem cell (MuSC), but the underlying mechanisms remain ill defined. In this study, we monitored mitophagy in MuSCS under various myogenic states and examined the role of PINK1 in maintaining regenerative capacity. Results indicate that quiescent MuSCs actively express mitophagy genes and exhibit a measurable mitophagy flux and prominent mitochondrial localization to autophagolysosomes, which become rapidly decreased during activation. Genetic disruption of Pink1 in mice reduces PARKIN recruitment to mitochondria and mitophagy in quiescent MuSCs, which is accompanied by premature activation/commitment at the expense of self-renewal and progressive loss of muscle regeneration, but unhindered proliferation and differentiation capacity. Results also show that impaired fate decisions in PINK1-deficient MuSCs can be restored by scavenging excess mitochondrial ROS. These data shed light on the regulation of mitophagy in MuSCs and position PINK1 as an important regulator of their mitochondrial properties and fate decisions.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857700","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 : 2024-05-14Epub Date: 2024-05-02DOI: 10.1016/j.stemcr.2024.04.002
Michela Lo Conte, Valeria Lucchino, Stefania Scalise, Clara Zannino, Desirèe Valente, Giada Rossignoli, Maria Stella Murfuni, Chiara Cicconetti, Luana Scaramuzzino, Danilo Swann Matassa, Anna Procopio, Graziano Martello, Giovanni Cuda, Elvira Immacolata Parrotta
{"title":"Unraveling the impact of ZZZ3 on the mTOR/ribosome pathway in human embryonic stem cells homeostasis.","authors":"Michela Lo Conte, Valeria Lucchino, Stefania Scalise, Clara Zannino, Desirèe Valente, Giada Rossignoli, Maria Stella Murfuni, Chiara Cicconetti, Luana Scaramuzzino, Danilo Swann Matassa, Anna Procopio, Graziano Martello, Giovanni Cuda, Elvira Immacolata Parrotta","doi":"10.1016/j.stemcr.2024.04.002","DOIUrl":"10.1016/j.stemcr.2024.04.002","url":null,"abstract":"<p><p>Embryonic stem cells (ESCs) are defined as stem cells with self-renewing and differentiation capabilities. These unique properties are tightly regulated and controlled by complex genetic and molecular mechanisms, whose understanding is essential for both basic and translational research. A large number of studies have mostly focused on understanding the molecular mechanisms governing pluripotency and differentiation of ESCs, while the regulation of proliferation has received comparably less attention. Here, we investigate the role of ZZZ3 (zinc finger ZZ-type containing 3) in human ESCs homeostasis. We found that knockdown of ZZZ3 negatively impacts ribosome biogenesis, translation, and mTOR signaling, leading to a significant reduction in cell proliferation. This process occurs without affecting pluripotency, suggesting that ZZZ3-depleted ESCs enter a \"dormant-like\" state and that proliferation and pluripotency can be uncoupled also in human ESCs.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858012","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 : 2024-05-01DOI: 10.1016/j.stemcr.2024.04.010
Pedro Rifes, Janko Kajtez, Josefine Rågård Christiansen, Alrik L. Schörling, Gaurav Singh Rathore, Daniel A Wolf, Andreas Heuer, A. Kirkeby
{"title":"Forced LMX1A expression induces dorsal neural fates and disrupts patterning of human embryonic stem cells into ventral midbrain dopaminergic neurons.","authors":"Pedro Rifes, Janko Kajtez, Josefine Rågård Christiansen, Alrik L. Schörling, Gaurav Singh Rathore, Daniel A Wolf, Andreas Heuer, A. Kirkeby","doi":"10.1016/j.stemcr.2024.04.010","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.04.010","url":null,"abstract":"","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141036169","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":"Restoration of fertility in nonablated recipient mice after spermatogonial stem cell transplantation.","authors":"Hiroko Morimoto, Narumi Ogonuki, Shogo Matoba, Mito Kanatsu-Shinohara, Atsuo Ogura, Takashi Shinohara","doi":"10.1016/j.stemcr.2024.02.003","DOIUrl":"10.1016/j.stemcr.2024.02.003","url":null,"abstract":"<p><p>Spermatogonial stem cell (SSC) transplantation is a valuable tool for studying stem cell-niche interaction. However, the conventional approach requires the removal of endogenous SSCs, causing damage to the niche. Here we introduce WIN18,446, an ALDH1A2 inhibitor, to enhance SSC colonization in nonablated recipients. Pre-transplantation treatment with WIN18,446 induced abnormal claudin protein expression, which comprises the blood-testis barrier and impedes SSC colonization. Consequently, WIN18,446 increased colonization efficiency by 4.6-fold compared with untreated host. WIN18,446-treated testes remained small despite the cessation of WIN18,446, suggesting its irreversible effect. Offspring were born by microinsemination using donor-derived sperm. While WIN18,446 was lethal to busulfan-treated mice, cyclophosphamide- or radiation-treated animals survived after WIN18,446 treatment. Although WIN18,446 is not applicable to humans due to toxicity, similar ALDH1A2 inhibitors may be useful for SSC transplantation into nonablated testes, shedding light on the role of retinoid metabolism on SSC-niche interactions and advancing SSC research in animal models and humans.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065984","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 : 2024-04-09Epub Date: 2024-03-21DOI: 10.1016/j.stemcr.2024.02.006
Michael W Ream, Lauren N Randolph, Yuqian Jiang, Yun Chang, Xiaoping Bao, Xiaojun Lance Lian
{"title":"Direct programming of human pluripotent stem cells into endothelial progenitors with SOX17 and FGF2.","authors":"Michael W Ream, Lauren N Randolph, Yuqian Jiang, Yun Chang, Xiaoping Bao, Xiaojun Lance Lian","doi":"10.1016/j.stemcr.2024.02.006","DOIUrl":"10.1016/j.stemcr.2024.02.006","url":null,"abstract":"<p><p>Transcription factors (TFs) are pivotal in guiding stem cell behavior, including their maintenance and differentiation. Using single-cell RNA sequencing, we investigated TFs expressed in endothelial progenitors (EPs) derived from human pluripotent stem cells (hPSCs) and identified upregulated expression of SOXF factors SOX7, SOX17, and SOX18 in the EP population. To test whether overexpression of these factors increases differentiation efficiency, we established inducible hPSC lines for each SOXF factor and found only SOX17 overexpression robustly increased the percentage of cells expressing CD34 and vascular endothelial cadherin (VEC). Conversely, SOX17 knockdown via CRISPR-Cas13d significantly compromised EP differentiation. Intriguingly, we discovered SOX17 overexpression alone was sufficient to generate CD34<sup>+</sup>VEC<sup>+</sup>CD31<sup>-</sup> cells, and, when combined with FGF2 treatment, more than 90% of CD34<sup>+</sup>VEC<sup>+</sup>CD31<sup>+</sup> EP was produced. These cells are capable of further differentiating into endothelial cells. These findings underscore an undiscovered role of SOX17 in programming hPSCs toward an EP lineage, illuminating pivotal mechanisms in EP differentiation.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190169","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 : 2024-04-09Epub Date: 2024-03-21DOI: 10.1016/j.stemcr.2024.02.007
Miriam Labusch, Melina Thetiot, Emmanuel Than-Trong, David Morizet, Marion Coolen, Hugo Varet, Rachel Legendre, Sara Ortica, Laure Mancini, Laure Bally-Cuif
{"title":"Prosaposin maintains adult neural stem cells in a state associated with deep quiescence.","authors":"Miriam Labusch, Melina Thetiot, Emmanuel Than-Trong, David Morizet, Marion Coolen, Hugo Varet, Rachel Legendre, Sara Ortica, Laure Mancini, Laure Bally-Cuif","doi":"10.1016/j.stemcr.2024.02.007","DOIUrl":"10.1016/j.stemcr.2024.02.007","url":null,"abstract":"<p><p>In most vertebrates, adult neural stem cells (NSCs) continuously give rise to neurons in discrete brain regions. A critical process for maintaining NSC pools over long periods of time in the adult brain is NSC quiescence, a reversible and tightly regulated state of cell-cycle arrest. Recently, lysosomes were identified to regulate the NSC quiescence-proliferation balance. However, it remains controversial whether lysosomal activity promotes NSC proliferation or quiescence, and a finer influence of lysosomal activity on NSC quiescence duration or depth remains unexplored. Using RNA sequencing and pharmacological manipulations, we show that lysosomes are necessary for NSC quiescence maintenance. In addition, we reveal that expression of psap, encoding the lysosomal regulator Prosaposin, is enriched in quiescent NSCs (qNSCs) that reside upstream in the NSC lineage and display a deep/long quiescence phase in the adult zebrafish telencephalon. We show that shRNA-mediated psap knockdown increases the proportion of activated NSCs (aNSCs) as well as NSCs that reside in shallower quiescence states (signed by ascl1a and deltaA expression). Collectively, our results identify the lysosomal protein Psap as a (direct or indirect) quiescence regulator and unfold the interplay between lysosomal function and NSC quiescence heterogeneities.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190171","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}