Cell stem cellPub Date : 2024-07-05DOI: 10.1016/j.stem.2024.06.010
Hao Wu, Jinglei Zhai, Hongmei Wang
{"title":"Unraveling the function of FGF signaling in human hypoblast specialization.","authors":"Hao Wu, Jinglei Zhai, Hongmei Wang","doi":"10.1016/j.stem.2024.06.010","DOIUrl":"10.1016/j.stem.2024.06.010","url":null,"abstract":"<p><p>Dattani et al.<sup>1</sup> developed a method for inducing hypoblast-like cells from human naive pluripotent stem cells. They elucidated the requirement for FGF signaling in human hypoblast specialization at a specific time window, which was previously controversial.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"31 7","pages":"945-946"},"PeriodicalIF":20.4,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2024-04-04Epub Date: 2024-03-15DOI: 10.1016/j.stem.2024.02.009
Maria C Basil, Konstantinos-Dionysios Alysandratos, Darrell N Kotton, Edward E Morrisey
{"title":"Lung repair and regeneration: Advanced models and insights into human disease.","authors":"Maria C Basil, Konstantinos-Dionysios Alysandratos, Darrell N Kotton, Edward E Morrisey","doi":"10.1016/j.stem.2024.02.009","DOIUrl":"10.1016/j.stem.2024.02.009","url":null,"abstract":"<p><p>The respiratory system acts as both the primary site of gas exchange and an important sensor and barrier to the external environment. The increase in incidences of respiratory disease over the past decades has highlighted the importance of developing improved therapeutic approaches. This review will summarize recent research on the cellular complexity of the mammalian respiratory system with a focus on gas exchange and immunological defense functions of the lung. Different models of repair and regeneration will be discussed to help interpret human and animal data and spur the investigation of models and assays for future drug development.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"439-454"},"PeriodicalIF":20.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11070171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2024-04-04Epub Date: 2024-03-26DOI: 10.1016/j.stem.2024.03.001
Adrian A Epstein, Sara N Janos, Luca Menozzi, Kelly Pegram, Vaibhav Jain, Logan C Bisset, Joseph T Davis, Samantha Morrison, Aswathy Shailaja, Yingqiu Guo, Agnes S Chao, Khadar Abdi, Blaire Rikard, Junjie Yao, Simon G Gregory, Kimberley Fisher, Rick Pittman, Al Erkanli, Kathryn E Gustafson, Caroline W T Carrico, William F Malcolm, Terrie E Inder, C Michael Cotten, Trevor D Burt, Mari L Shinohara, Charles M Maxfield, Eric J Benner
{"title":"Subventricular zone stem cell niche injury is associated with intestinal perforation in preterm infants and predicts future motor impairment.","authors":"Adrian A Epstein, Sara N Janos, Luca Menozzi, Kelly Pegram, Vaibhav Jain, Logan C Bisset, Joseph T Davis, Samantha Morrison, Aswathy Shailaja, Yingqiu Guo, Agnes S Chao, Khadar Abdi, Blaire Rikard, Junjie Yao, Simon G Gregory, Kimberley Fisher, Rick Pittman, Al Erkanli, Kathryn E Gustafson, Caroline W T Carrico, William F Malcolm, Terrie E Inder, C Michael Cotten, Trevor D Burt, Mari L Shinohara, Charles M Maxfield, Eric J Benner","doi":"10.1016/j.stem.2024.03.001","DOIUrl":"10.1016/j.stem.2024.03.001","url":null,"abstract":"<p><p>Brain injury is highly associated with preterm birth. Complications of prematurity, including spontaneous or necrotizing enterocolitis (NEC)-associated intestinal perforations, are linked to lifelong neurologic impairment, yet the mechanisms are poorly understood. Early diagnosis of preterm brain injuries remains a significant challenge. Here, we identified subventricular zone echogenicity (SVE) on cranial ultrasound in preterm infants following intestinal perforations. The development of SVE was significantly associated with motor impairment at 2 years. SVE was replicated in a neonatal mouse model of intestinal perforation. Examination of the murine echogenic subventricular zone (SVZ) revealed NLRP3-inflammasome assembly in multiciliated FoxJ1<sup>+</sup> ependymal cells and a loss of the ependymal border in this postnatal stem cell niche. These data suggest a mechanism of preterm brain injury localized to the SVZ that has not been adequately considered. Ultrasound detection of SVE may serve as an early biomarker for neurodevelopmental impairment after inflammatory disease in preterm infants.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"467-483.e6"},"PeriodicalIF":20.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11129818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2024-04-04Epub Date: 2024-03-07DOI: 10.1016/j.stem.2024.02.005
Xiang Yuan, Jingqi Wu, Zhen Sun, Jin Cen, Yajing Shu, Chenhua Wang, Hong Li, Dongni Lin, Kun Zhang, Baihua Wu, Anil Dhawan, Ludi Zhang, Lijian Hui
{"title":"Preclinical efficacy and safety of encapsulated proliferating human hepatocyte organoids in treating liver failure.","authors":"Xiang Yuan, Jingqi Wu, Zhen Sun, Jin Cen, Yajing Shu, Chenhua Wang, Hong Li, Dongni Lin, Kun Zhang, Baihua Wu, Anil Dhawan, Ludi Zhang, Lijian Hui","doi":"10.1016/j.stem.2024.02.005","DOIUrl":"10.1016/j.stem.2024.02.005","url":null,"abstract":"<p><p>Alginate-encapsulated hepatocyte transplantation is a promising strategy to treat liver failure. However, its clinical application was impeded by the lack of primary human hepatocytes and difficulty in controlling their quality. We previously reported proliferating human hepatocytes (ProliHHs). Here, quality-controlled ProliHHs were produced in mass and engineered as liver organoids to improve their maturity. Encapsulated ProliHHs liver organoids (eLO) were intraperitoneally transplanted to treat liver failure animals. Notably, eLO treatment increased the survival of mice with post-hepatectomy liver failure (PHLF) and ameliorated hyperammonemia and hypoglycemia by providing liver functions. Additionally, eLO treatment protected the gut from PHLF-augmented permeability and normalized the increased serum endotoxin and inflammatory response, which facilitated liver regeneration. The therapeutic effect of eLO was additionally proved in acetaminophen-induced liver failure. Furthermore, we performed assessments of toxicity and biodistribution, demonstrating that eLO had no adverse effects on animals and remained non-tumorigenic.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"484-498.e5"},"PeriodicalIF":20.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2024-04-04Epub Date: 2024-03-22DOI: 10.1016/j.stem.2024.02.011
Christopher S Morrow, Kelsey Tweed, Sabina Farhadova, Alex J Walsh, Bo P Lear, Avtar Roopra, Ryan D Risgaard, Payton C Klosa, Zachary P Arndt, Ella R Peterson, Michelle M Chi, Allison G Harris, Melissa C Skala, Darcie L Moore
{"title":"Autofluorescence is a biomarker of neural stem cell activation state.","authors":"Christopher S Morrow, Kelsey Tweed, Sabina Farhadova, Alex J Walsh, Bo P Lear, Avtar Roopra, Ryan D Risgaard, Payton C Klosa, Zachary P Arndt, Ella R Peterson, Michelle M Chi, Allison G Harris, Melissa C Skala, Darcie L Moore","doi":"10.1016/j.stem.2024.02.011","DOIUrl":"10.1016/j.stem.2024.02.011","url":null,"abstract":"<p><p>Neural stem cells (NSCs) must exit quiescence to produce neurons; however, our understanding of this process remains constrained by the technical limitations of current technologies. Fluorescence lifetime imaging (FLIM) of autofluorescent metabolic cofactors has been used in other cell types to study shifts in cell states driven by metabolic remodeling that change the optical properties of these endogenous fluorophores. Using this non-destructive, live-cell, and label-free strategy, we found that quiescent NSCs (qNSCs) and activated NSCs (aNSCs) have unique autofluorescence profiles. Specifically, qNSCs display an enrichment of autofluorescence localizing to a subset of lysosomes, which can be used as a graded marker of NSC quiescence to predict cell behavior at single-cell resolution. Coupling autofluorescence imaging with single-cell RNA sequencing, we provide resources revealing transcriptional features linked to deep quiescence and rapid NSC activation. Together, we describe an approach for tracking mouse NSC activation state and expand our understanding of adult neurogenesis.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"570-581.e7"},"PeriodicalIF":20.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140195314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques.","authors":"Byung-Chul Lee, Ashley Gin, Chuanfeng Wu, Komudi Singh, Max Grice, Ryland Mortlock, Diana Abraham, Xing Fan, Yifan Zhou, Aisha AlJanahi, Uimook Choi, Suk See DeRavin, Taehoon Shin, Sogun Hong, Cynthia E Dunbar","doi":"10.1016/j.stem.2024.02.010","DOIUrl":"10.1016/j.stem.2024.02.010","url":null,"abstract":"<p><p>For precise genome editing via CRISPR/homology-directed repair (HDR), effective and safe editing of long-term engrafting hematopoietic stem cells (LT-HSCs) is required. The impact of HDR on true LT-HSC clonal dynamics in a relevant large animal model has not been studied. To track the output and clonality of HDR-edited cells and to provide a comparison to lentivirally transduced HSCs in vivo, we developed a competitive rhesus macaque (RM) autologous transplantation model, co-infusing HSCs transduced with a barcoded GFP-expressing lentiviral vector (LV) and HDR edited at the CD33 locus. CRISPR/HDR-edited cells showed a two-log decrease by 2 months following transplantation, with little improvement via p53 inhibition, in comparison to minimal loss of LV-transduced cells long term. HDR long-term clonality was oligoclonal in contrast to highly polyclonal LV-transduced HSCs. These results suggest marked clinically relevant differences in the impact of current genetic modification approaches on HSCs.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"455-466.e4"},"PeriodicalIF":20.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2024-03-07Epub Date: 2024-02-15DOI: 10.1016/j.stem.2024.01.007
Kavita Raniga, Aishah Nasir, Nguyen T N Vo, Ravi Vaidyanathan, Sarah Dickerson, Simon Hilcove, Diogo Mosqueira, Gary R Mirams, Peter Clements, Ryan Hicks, Amy Pointon, Will Stebbeds, Jo Francis, Chris Denning
{"title":"Strengthening cardiac therapy pipelines using human pluripotent stem cell-derived cardiomyocytes.","authors":"Kavita Raniga, Aishah Nasir, Nguyen T N Vo, Ravi Vaidyanathan, Sarah Dickerson, Simon Hilcove, Diogo Mosqueira, Gary R Mirams, Peter Clements, Ryan Hicks, Amy Pointon, Will Stebbeds, Jo Francis, Chris Denning","doi":"10.1016/j.stem.2024.01.007","DOIUrl":"10.1016/j.stem.2024.01.007","url":null,"abstract":"<p><p>Advances in hiPSC isolation and reprogramming and hPSC-CM differentiation have prompted their therapeutic application and utilization for evaluating potential cardiovascular safety liabilities. In this perspective, we showcase key efforts toward the large-scale production of hiPSC-CMs, implementation of hiPSC-CMs in industry settings, and recent clinical applications of this technology. The key observations are a need for traceable gender and ethnically diverse hiPSC lines, approaches to reduce cost of scale-up, accessible clinical trial datasets, and transparent guidelines surrounding the safety and efficacy of hiPSC-based therapies.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"292-311"},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2024-03-07Epub Date: 2024-02-08DOI: 10.1016/j.stem.2024.02.001
Xiaomeng Hu, Kathy White, Chi Young, Ari G Olroyd, Paul Kievit, Andrew J Connolly, Tobias Deuse, Sonja Schrepfer
{"title":"Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate.","authors":"Xiaomeng Hu, Kathy White, Chi Young, Ari G Olroyd, Paul Kievit, Andrew J Connolly, Tobias Deuse, Sonja Schrepfer","doi":"10.1016/j.stem.2024.02.001","DOIUrl":"10.1016/j.stem.2024.02.001","url":null,"abstract":"<p><p>Allogeneic transplantation of pancreatic islets for patients with difficult-to-control diabetes mellitus is severely hampered by the requirement for continuous immunosuppression and its associated morbidity. We report that allogeneic transplantation of genetically engineered (B2M<sup>-/-</sup>, CIITA<sup>-/-</sup>, CD47<sup>+</sup>), primary, hypoimmune, pseudo-islets (p-islets) results in their engraftment into a fully immunocompetent, diabetic non-human primate wherein they provide stable endocrine function and enable insulin independence without inducing any detectable immune response in the absence of immunosuppression. Hypoimmune primary p-islets may provide a curative cell therapy for type 1 diabetes mellitus.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"334-340.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2024-03-07DOI: 10.1016/j.stem.2024.02.006
Mallory Ryan, Justin A McDonough, Michael E Ward, Mark R Cookson, William C Skarnes, Florian T Merkle
{"title":"Large structural variants in KOLF2.1J are unlikely to compromise neurological disease modeling.","authors":"Mallory Ryan, Justin A McDonough, Michael E Ward, Mark R Cookson, William C Skarnes, Florian T Merkle","doi":"10.1016/j.stem.2024.02.006","DOIUrl":"10.1016/j.stem.2024.02.006","url":null,"abstract":"","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"31 3","pages":"290-291"},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell stem cellPub Date : 2024-03-07DOI: 10.1016/j.stem.2024.02.004
Massimo Bonora, Claudia Morganti, Nick van Gastel, Kyoko Ito, Enrica Calura, Ilaria Zanolla, Letizia Ferroni, Yang Zhang, Yookyung Jung, Gabriele Sales, Paolo Martini, Takahisa Nakamura, Francesco Massimo Lasorsa, Toren Finkel, Charles P Lin, Barbara Zavan, Paolo Pinton, Irene Georgakoudi, Chiara Romualdi, David T Scadden, Keisuke Ito
{"title":"A mitochondrial NADPH-cholesterol axis regulates extracellular vesicle biogenesis to support hematopoietic stem cell fate.","authors":"Massimo Bonora, Claudia Morganti, Nick van Gastel, Kyoko Ito, Enrica Calura, Ilaria Zanolla, Letizia Ferroni, Yang Zhang, Yookyung Jung, Gabriele Sales, Paolo Martini, Takahisa Nakamura, Francesco Massimo Lasorsa, Toren Finkel, Charles P Lin, Barbara Zavan, Paolo Pinton, Irene Georgakoudi, Chiara Romualdi, David T Scadden, Keisuke Ito","doi":"10.1016/j.stem.2024.02.004","DOIUrl":"10.1016/j.stem.2024.02.004","url":null,"abstract":"<p><p>Mitochondrial fatty acid oxidation (FAO) is essential for hematopoietic stem cell (HSC) self-renewal; however, the mechanism by which mitochondrial metabolism controls HSC fate remains unknown. Here, we show that within the hematopoietic lineage, HSCs have the largest mitochondrial NADPH pools, which are required for proper HSC cell fate and homeostasis. Bioinformatic analysis of the HSC transcriptome, biochemical assays, and genetic inactivation of FAO all indicate that FAO-generated NADPH fuels cholesterol synthesis in HSCs. Interference with FAO disturbs the segregation of mitochondrial NADPH toward corresponding daughter cells upon single HSC division. Importantly, we have found that the FAO-NADPH-cholesterol axis drives extracellular vesicle (EV) biogenesis and release in HSCs, while inhibition of EV signaling impairs HSC self-renewal. These data reveal the existence of a mitochondrial NADPH-cholesterol axis for EV biogenesis that is required for hematopoietic homeostasis and highlight the non-stochastic nature of HSC fate determination.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"31 3","pages":"359-377.e10"},"PeriodicalIF":20.4,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10957094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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