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Patient iPSC models reveal glia-intrinsic phenotypes in multiple sclerosis. 患者 iPSC 模型揭示了多发性硬化症的神经胶质内表型。
Cell stem cell Pub Date : 2024-11-07 Epub Date: 2024-08-26 DOI: 10.1016/j.stem.2024.08.002
Benjamin L L Clayton, Lilianne Barbar, Maria Sapar, Kriti Kalpana, Chandrika Rao, Bianca Migliori, Tomasz Rusielewicz, Daniel Paull, Katie Brenner, Dorota Moroziewicz, Ilana Katz Sand, Patrizia Casaccia, Paul J Tesar, Valentina Fossati
{"title":"Patient iPSC models reveal glia-intrinsic phenotypes in multiple sclerosis.","authors":"Benjamin L L Clayton, Lilianne Barbar, Maria Sapar, Kriti Kalpana, Chandrika Rao, Bianca Migliori, Tomasz Rusielewicz, Daniel Paull, Katie Brenner, Dorota Moroziewicz, Ilana Katz Sand, Patrizia Casaccia, Paul J Tesar, Valentina Fossati","doi":"10.1016/j.stem.2024.08.002","DOIUrl":"10.1016/j.stem.2024.08.002","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS), resulting in neurological disability that worsens over time. While progress has been made in defining the immune system's role in MS pathophysiology, the contribution of intrinsic CNS cell dysfunction remains unclear. Here, we generated a collection of induced pluripotent stem cell (iPSC) lines from people with MS spanning diverse clinical subtypes and differentiated them into glia-enriched cultures. Using single-cell transcriptomic profiling and orthogonal analyses, we observed several distinguishing characteristics of MS cultures pointing to glia-intrinsic disease mechanisms. We found that primary progressive MS-derived cultures contained fewer oligodendrocytes. Moreover, MS-derived oligodendrocyte lineage cells and astrocytes showed increased expression of immune and inflammatory genes, matching those of glia from MS postmortem brains. Thus, iPSC-derived MS models provide a unique platform for dissecting glial contributions to disease phenotypes independent of the peripheral immune system and identify potential glia-specific targets for therapeutic intervention.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1701-1713.e8"},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082836","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}
引用次数: 0
Hallmarks of regeneration. 再生的标志
Cell stem cell Pub Date : 2024-09-05 Epub Date: 2024-08-19 DOI: 10.1016/j.stem.2024.07.007
Kenneth D Poss, Elly M Tanaka
{"title":"Hallmarks of regeneration.","authors":"Kenneth D Poss, Elly M Tanaka","doi":"10.1016/j.stem.2024.07.007","DOIUrl":"10.1016/j.stem.2024.07.007","url":null,"abstract":"<p><p>Regeneration is a heroic biological process that restores tissue architecture and function in the face of day-to-day cell loss or the aftershock of injury. Capacities and mechanisms for regeneration can vary widely among species, organs, and injury contexts. Here, we describe \"hallmarks\" of regeneration found in diverse settings of the animal kingdom, including activation of a cell source, initiation of regenerative programs in the source, interplay with supporting cell types, and control of tissue size and function. We discuss these hallmarks with an eye toward major challenges and applications of regenerative biology.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1244-1261"},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11410156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010120","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}
引用次数: 0
Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells. 单细胞综合分析确定了耐阉割前列腺管腔细胞的表观遗传学基础。
Cell stem cell Pub Date : 2024-08-01 Epub Date: 2024-06-14 DOI: 10.1016/j.stem.2024.05.008
Jason S Kirk, Jie Wang, Mark Long, Spencer Rosario, Amanda Tracz, Yibing Ji, Rahul Kumar, Xiaozhuo Liu, Anmbreen Jamroze, Prashant K Singh, Igor Puzanov, Gurkamal Chatta, Qing Cheng, Jiaoti Huang, Jeffrey L Wrana, Jonathan Lovell, Han Yu, Song Liu, Michael M Shen, Tao Liu, Dean G Tang
{"title":"Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells.","authors":"Jason S Kirk, Jie Wang, Mark Long, Spencer Rosario, Amanda Tracz, Yibing Ji, Rahul Kumar, Xiaozhuo Liu, Anmbreen Jamroze, Prashant K Singh, Igor Puzanov, Gurkamal Chatta, Qing Cheng, Jiaoti Huang, Jeffrey L Wrana, Jonathan Lovell, Han Yu, Song Liu, Michael M Shen, Tao Liu, Dean G Tang","doi":"10.1016/j.stem.2024.05.008","DOIUrl":"10.1016/j.stem.2024.05.008","url":null,"abstract":"<p><p>Understanding prostate response to castration and androgen receptor signaling inhibitors (ARSI) is critical to improving long-term prostate cancer (PCa) patient survival. Here, we use a multi-omics approach on 229,794 single cells to create a mouse single-cell reference atlas for interpreting mouse prostate biology and castration response. Our reference atlas refines single-cell annotations and provides a chromatin context, which, when coupled with mouse lineage tracing, demonstrates that castration-resistant luminal cells are distinct from the pre-existent urethra-proximal stem/progenitor cells. Molecular pathway analysis and therapeutic studies further implicate AP1 (JUN/FOS), WNT/β-catenin, FOXQ1, NF-κB, and JAK/STAT pathways as major drivers of castration-resistant luminal populations with relevance to human PCa. Our datasets, which can be explored through an interactive portal (https://visportal.roswellpark.org/data/tang/), can aid in developing combination treatments with ARSI for advanced PCa patients.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1203-1221.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328143","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}
引用次数: 0
Oscillation steers differentiation. 震荡引导分化。
Cell stem cell Pub Date : 2024-07-05 DOI: 10.1016/j.stem.2024.06.008
Kyle A LaBella, Efren A Reyes, Louis Vermeulen
{"title":"Oscillation steers differentiation.","authors":"Kyle A LaBella, Efren A Reyes, Louis Vermeulen","doi":"10.1016/j.stem.2024.06.008","DOIUrl":"https://doi.org/10.1016/j.stem.2024.06.008","url":null,"abstract":"<p><p>The differentiation trajectories defining enteroendocrine (EE) cell heterogeneity remain obscure. In this issue of Cell Stem Cell, Singh et al.<sup>1</sup> map the differentiation landscape of EE cells, identifying early oscillating cell progenitor states, which play a critical role in generating terminal EE cell diversity.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"31 7","pages":"943-945"},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545709","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}
引用次数: 0
Monkey see, monkey do: Tracking iPS-cardiomyocyte survival and maturation in autografts. 猴子看，猴子干：跟踪 iPS 心肌细胞在自体移植物中的存活和成熟。
Cell stem cell Pub Date : 2024-07-05 DOI: 10.1016/j.stem.2024.06.006
Xiaoqian Ji, Qiyuan Wang, Nan Cao
{"title":"Monkey see, monkey do: Tracking iPS-cardiomyocyte survival and maturation in autografts.","authors":"Xiaoqian Ji, Qiyuan Wang, Nan Cao","doi":"10.1016/j.stem.2024.06.006","DOIUrl":"https://doi.org/10.1016/j.stem.2024.06.006","url":null,"abstract":"<p><p>Induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) therapy has emerged as a highly promising field of heart repair. Lin et al.<sup>1</sup> presented compelling evidence on the long-term engraftment and maturation of autologous iPSC-CMs in two rhesus macaques, demonstrating unprecedented cardiac autografting data in large animal models without the need of immunosuppressants.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"31 7","pages":"941-943"},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545708","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}
引用次数: 0
Cultivating awareness of donation in cutting-edge allogenic cell therapies. 在最前沿的异基因细胞疗法中培养捐赠意识。
Cell stem cell Pub Date : 2024-07-05 DOI: 10.1016/j.stem.2024.06.002
Oscar Andrusier, Aviad Raz, Jusaku Minari
{"title":"Cultivating awareness of donation in cutting-edge allogenic cell therapies.","authors":"Oscar Andrusier, Aviad Raz, Jusaku Minari","doi":"10.1016/j.stem.2024.06.002","DOIUrl":"https://doi.org/10.1016/j.stem.2024.06.002","url":null,"abstract":"","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"31 7","pages":"947-948"},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545707","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}
引用次数: 0
Activation of fetal-like molecular programs during regeneration in the intestine and beyond. 在肠道再生及其他过程中激活胎儿样分子程序
Cell stem cell Pub Date : 2024-07-05 DOI: 10.1016/j.stem.2024.05.009
Sara Viragova, Dong Li, Ophir D Klein
{"title":"Activation of fetal-like molecular programs during regeneration in the intestine and beyond.","authors":"Sara Viragova, Dong Li, Ophir D Klein","doi":"10.1016/j.stem.2024.05.009","DOIUrl":"10.1016/j.stem.2024.05.009","url":null,"abstract":"<p><p>Tissue regeneration after damage is generally thought to involve the mobilization of adult stem cells that divide and differentiate into progressively specialized progeny. However, recent studies indicate that tissue regeneration can be accompanied by reversion to a fetal-like state. During this process, cells at the injury site reactivate programs that operate during fetal development but are typically absent in adult homeostasis. Here, we summarize our current understanding of the molecular signals and epigenetic mediators that orchestrate \"fetal-like reversion\" during intestinal regeneration. We also explore evidence for this phenomenon in other organs and species and highlight open questions that merit future examination.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"31 7","pages":"949-960"},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11235077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545706","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}
引用次数: 0
Unraveling the function of FGF signaling in human hypoblast specialization. 揭示 FGF 信号在人类低分化母细胞特化过程中的功能。
Cell stem cell Pub Date : 2024-07-05 DOI: 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":"https://doi.org/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":0.0,"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}
引用次数: 0
Subventricular zone stem cell niche injury is associated with intestinal perforation in preterm infants and predicts future motor impairment. 脑室下区干细胞龛损伤与早产儿肠穿孔有关，并可预测未来的运动障碍。
Cell stem cell Pub Date : 2024-04-04 Epub Date: 2024-03-26 DOI: 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":0.0,"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}
引用次数: 0
Lung repair and regeneration: Advanced models and insights into human disease. 肺修复与再生：先进的模型和对人类疾病的见解。
Cell stem cell Pub Date : 2024-04-04 Epub Date: 2024-03-15 DOI: 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":0.0,"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}
引用次数: 0
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