Cell stem cellPub Date : 2025-02-06DOI: 10.1016/j.stem.2025.01.004
Yi Wang, Zhong Chen
{"title":"Cognitive impairment in epilepsy progression: Adult neurogenesis loss at critical window","authors":"Yi Wang, Zhong Chen","doi":"10.1016/j.stem.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.004","url":null,"abstract":"The mechanisms underlying cognitive impairment in epilepsy remain poorly understood. Ammothumkandy et al.<span><span><sup>1</sup></span></span> reveal that the loss of adult immature neurons correlates with auditory verbal learning deficits in human mesial temporal lobe epilepsy during a critical disease period, underscoring the pivotal role of adult neurogenesis in specific cognitive domain.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"66 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2025-02-06DOI: 10.1016/j.stem.2025.01.008
Stefanie DeFronzo, Guohao Dai
{"title":"Human iPSCs offer an alternative for modeling vascular malformation","authors":"Stefanie DeFronzo, Guohao Dai","doi":"10.1016/j.stem.2025.01.008","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.008","url":null,"abstract":"In this issue of <em>Cell Stem Cell</em>, Pan et al. generated human induced pluripotent stem cell (iPSC)-derived venous endothelial cells (iVECs) by manipulating cell-cycle dynamics and Notch signaling and demonstrated that TIE2-mutant iVECs recapitulate the pathogenesis of venous malformations.<span><span><sup>1</sup></span></span> Their study provides a model for further mechanistic studies and drug discovery.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"62 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2025-02-06DOI: 10.1016/j.stem.2025.01.001
Alina Marymonchyk, Raquel Rodriguez-Aller, Ashleigh Willis, Frédéric Beaupré, Sareen Warsi, Marina Snapyan, Valérie Clavet-Fournier, Flavie Lavoie-Cardinal, David R. Kaplan, Freda D. Miller, Armen Saghatelyan
{"title":"Neural stem cell quiescence and activation dynamics are regulated by feedback input from their progeny under homeostatic and regenerative conditions","authors":"Alina Marymonchyk, Raquel Rodriguez-Aller, Ashleigh Willis, Frédéric Beaupré, Sareen Warsi, Marina Snapyan, Valérie Clavet-Fournier, Flavie Lavoie-Cardinal, David R. Kaplan, Freda D. Miller, Armen Saghatelyan","doi":"10.1016/j.stem.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.001","url":null,"abstract":"Life-long maintenance of stem cells implies that feedback mechanisms from the niche regulate their quiescence/activation dynamics. Here, in the mouse adult subventricular neural stem cell (NSC) niche, we charted a precise spatiotemporal map of functional responses in NSCs induced by multiple niche cells and used machine learning to predict NSC interactions with specific niche cell types. We revealed a feedback mechanism whereby the NSC proliferative state is directly repressed by transient amplifying cells (TAPs), their rapidly dividing progeny. NSC processes wrap around TAPs and display hotspots of Ca<sup>2+</sup> activity at their points of contact, mediated by ephrin (Efn) signaling. The modulation of Efn signaling or TAP ablation altered the Ca<sup>2+</sup> signature of NSCs, leading to their activation. <em>In vivo</em> optogenetic modulation of Ca<sup>2+</sup> dynamics abrogated NSC activation and prevented niche replenishment. Thus, TAP-to-NSC feedback signaling controls stem cell quiescence and activation, providing a mechanism to maintain stem cell pools throughout life.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"42 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2025-02-06DOI: 10.1016/j.stem.2025.01.009
Chenyan Huang, Ai Ing Lim
{"title":"Pre-birth stem cell education: A gift from mother’s bugs","authors":"Chenyan Huang, Ai Ing Lim","doi":"10.1016/j.stem.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.009","url":null,"abstract":"The maternal gut microbiota undergoes significant changes during pregnancy and plays a pivotal role in offspring development. In this issue, Dang et al. demonstrate that modifying the maternal gut microbiome during pregnancy shapes offspring neural and intestinal stem cells via the mTOR pathway, with long-lasting effects on their functions.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"9 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2025-02-06DOI: 10.1016/j.stem.2024.12.009
Giulia Hardouin, Annarita Miccio
{"title":"Two is better than one: Advancing gene therapy protocols for enhanced safety and efficacy","authors":"Giulia Hardouin, Annarita Miccio","doi":"10.1016/j.stem.2024.12.009","DOIUrl":"https://doi.org/10.1016/j.stem.2024.12.009","url":null,"abstract":"In this issue of <em>Cell Stem Cell</em>, two complementary studies from Zeng et al.<span><span><sup>1</sup></span></span> and Demirci et al.<span><span><sup>2</sup></span></span> improve the efficacy of gene therapy for β-hemoglobinopathies using multiplex CRISPR-Cas9 editing. The authors also optimize editing and conditioning protocols to reduce risks associated with current gene therapy procedures.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"15 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2025-02-04DOI: 10.1016/j.stem.2024.12.011
Katarzyna Ciuba, Aleksandra Piotrowska, Debadeep Chaudhury, Bondita Dehingia, Eryk Duński, Rüdiger Behr, Karolina Soroczyńska, Małgorzata Czystowska-Kuźmicz, Misbah Abbas, Edyta Bulanda, Sylwia Gawlik-Zawiślak, Sylwia Pietrzak, Izabela Figiel, Jakub Włodarczyk, Alexei Verkhratsky, Marcin Niedbała, Wojciech Kaspera, Tomasz Wypych, Bartosz Wilczyński, Aleksandra Pękowska
{"title":"Molecular signature of primate astrocytes reveals pathways and regulatory changes contributing to human brain evolution","authors":"Katarzyna Ciuba, Aleksandra Piotrowska, Debadeep Chaudhury, Bondita Dehingia, Eryk Duński, Rüdiger Behr, Karolina Soroczyńska, Małgorzata Czystowska-Kuźmicz, Misbah Abbas, Edyta Bulanda, Sylwia Gawlik-Zawiślak, Sylwia Pietrzak, Izabela Figiel, Jakub Włodarczyk, Alexei Verkhratsky, Marcin Niedbała, Wojciech Kaspera, Tomasz Wypych, Bartosz Wilczyński, Aleksandra Pękowska","doi":"10.1016/j.stem.2024.12.011","DOIUrl":"https://doi.org/10.1016/j.stem.2024.12.011","url":null,"abstract":"Astrocytes contribute to the development and regulation of the higher-level functions of the brain, the critical targets of evolution. However, how astrocytes evolve in primates is unsettled. Here, we obtain human, chimpanzee, and macaque induced pluripotent stem-cell-derived astrocytes (iAstrocytes). Human iAstrocytes are bigger and more complex than the non-human primate iAstrocytes. We identify new loci contributing to the increased human astrocyte. We show that genes and pathways implicated in long-range intercellular signaling are activated in the human iAstrocytes and partake in controlling iAstrocyte complexity. Genes downregulated in human iAstrocytes frequently relate to neurological disorders and were decreased in adult brain samples. Through regulome analysis and machine learning, we uncover that functional activation of enhancers coincides with a previously unappreciated, pervasive gain of “stripe” transcription factor binding sites. Altogether, we reveal the transcriptomic signature of primate astrocyte evolution and a mechanism driving the acquisition of the regulatory potential of enhancers.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"84 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adult bi-paternal offspring generated through direct modification of imprinted genes in mammals","authors":"Zhi-kun Li, Li-bin Wang, Le-yun Wang, Xue-han Sun, Ze-hui Ren, Si-nan Ma, Yu-long Zhao, Chao Liu, Gui-hai Feng, Tao Liu, Tian-shi Pan, Qing-tong Shan, Kai Xu, Guan-zheng Luo, Qi Zhou, Wei Li","doi":"10.1016/j.stem.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.005","url":null,"abstract":"Imprinting abnormalities pose a significant challenge in applications involving embryonic stem cells, induced pluripotent stem cells, and animal cloning, with no universal correction method owing to their complexity and stochastic nature. In this study, we targeted these defects at their source—embryos from same-sex parents—aiming to establish a stable, maintainable imprinting pattern <em>de novo</em> in mammalian cells. Using bi-paternal mouse embryos, which exhibit severe imprinting defects and are typically non-viable, we introduced frameshift mutations, gene deletions, and regulatory edits at 20 key imprinted loci, ultimately achieving the development of fully adult animals, albeit with a relatively low survival rate. The findings provide strong evidence that imprinting abnormalities are a primary barrier to unisexual reproduction in mammals. Moreover, this approach can significantly improve developmental outcomes for embryonic stem cells and cloned animals, opening promising avenues for advancements in regenerative medicine.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"39 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2025-01-17DOI: 10.1016/j.stem.2024.12.006
Bing Peng, Qingyi Wang, Feixiang Zhang, Hui Shen, Peng Du
{"title":"Mouse totipotent blastomere-like cells model embryogenesis from zygotic genome activation to post implantation","authors":"Bing Peng, Qingyi Wang, Feixiang Zhang, Hui Shen, Peng Du","doi":"10.1016/j.stem.2024.12.006","DOIUrl":"https://doi.org/10.1016/j.stem.2024.12.006","url":null,"abstract":"Embryo development begins with zygotic genome activation (ZGA), eventually generating blastocysts for implantation. However, <em>in vitro</em> systems modeling the pre-implantation development are still absent and challenging. Here, we used mouse totipotent blastomere-like cells (TBLCs) to develop spontaneous differentiation and blastoid formation systems, respectively. We found Wnt signaling enabled the rapid expansion of TBLCs and the optimization of their culture medium. We successfully developed a TBLC-spontaneous differentiation system in which mouse TBLCs (mTBLCs) firstly converted into two types of ZGA-like cells (ZLCs) distinguished by Zscan4 expression. Surprisingly, Zscan4-, but not Zscan4+, ZLCs further passed through intermediate 4-cell and then 8-cell/morula stages to produce epiblast, primitive endoderm, and trophectoderm lineages. Significantly, single TBLCs underwent expansion, compaction, and polarization to efficiently generate blastocyst-like structures and even post-implantation egg-cylinder-like structures. Conclusively, we established TBLC-based differentiation and embryo-like structure formation systems to model early embryonic development, offering criteria for evaluating and understanding totipotency.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"27 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}