Cell stem cellPub Date : 2024-03-07DOI: 10.1016/j.stem.2024.02.007
Carolina Gracia-Diaz, Jonathan E Perdomo, Munir E Khan, Thomas Roule, Brianna L Disanza, Gregory G Cajka, Sunyimeng Lei, Alyssa L Gagne, Jean Ann Maguire, Ophir Shalem, Elizabeth J Bhoj, Rebecca C Ahrens-Nicklas, Deborah L French, Ethan M Goldberg, Kai Wang, Joseph T Glessner, Naiara Akizu
{"title":"KOLF2.1J iPSCs carry CNVs associated with neurodevelopmental disorders.","authors":"Carolina Gracia-Diaz, Jonathan E Perdomo, Munir E Khan, Thomas Roule, Brianna L Disanza, Gregory G Cajka, Sunyimeng Lei, Alyssa L Gagne, Jean Ann Maguire, Ophir Shalem, Elizabeth J Bhoj, Rebecca C Ahrens-Nicklas, Deborah L French, Ethan M Goldberg, Kai Wang, Joseph T Glessner, Naiara Akizu","doi":"10.1016/j.stem.2024.02.007","DOIUrl":"10.1016/j.stem.2024.02.007","url":null,"abstract":"","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"31 3","pages":"288-289"},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066373","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: 2024-02-15DOI: 10.1016/j.stem.2024.01.008
Chenxi Ye, Chuanlai Yang, Heqiang Zhang, Rui Gao, Yingnan Liao, Yali Zhang, Lingjun Jie, Yanhui Zhang, Tong Cheng, Yan Wang, Jie Ren
{"title":"Canonical Wnt signaling directs the generation of functional human PSC-derived atrioventricular canal cardiomyocytes in bioprinted cardiac tissues.","authors":"Chenxi Ye, Chuanlai Yang, Heqiang Zhang, Rui Gao, Yingnan Liao, Yali Zhang, Lingjun Jie, Yanhui Zhang, Tong Cheng, Yan Wang, Jie Ren","doi":"10.1016/j.stem.2024.01.008","DOIUrl":"10.1016/j.stem.2024.01.008","url":null,"abstract":"<p><p>The creation of a functional 3D bioprinted human heart remains challenging, largely due to the lack of some crucial cardiac cell types, including the atrioventricular canal (AVC) cardiomyocytes, which are essential to slow down the electrical impulse between the atrium and ventricle. By utilizing single-cell RNA sequencing analysis and a 3D bioprinting technology, we discover that stage-specific activation of canonical Wnt signaling creates functional AVC cardiomyocytes derived from human pluripotent stem cells. These cardiomyocytes display morphological characteristics and express molecular markers of AVC cardiomyocytes, including transcription factors TBX2 and MSX2. When bioprinted in prefabricated cardiac tissues, these cardiomyocytes successfully delay the electrical impulse, demonstrating their capability of functioning as the AVC cardiomyocytes in vitro. Thus, these findings not only identify canonical Wnt signaling as a key regulator of the AVC cardiomyocyte differentiation in vitro, but, more importantly, provide a critical cellular source for the biofabrication of a functional human heart.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"398-409.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747960","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 : 2024-02-01Epub Date: 2024-01-05DOI: 10.1016/j.stem.2023.12.001
Iwo Kucinski, Joana Campos, Melania Barile, Francesco Severi, Natacha Bohin, Pedro N Moreira, Lewis Allen, Hannah Lawson, Myriam L R Haltalli, Sarah J Kinston, Dónal O'Carroll, Kamil R Kranc, Berthold Göttgens
{"title":"A time- and single-cell-resolved model of murine bone marrow hematopoiesis.","authors":"Iwo Kucinski, Joana Campos, Melania Barile, Francesco Severi, Natacha Bohin, Pedro N Moreira, Lewis Allen, Hannah Lawson, Myriam L R Haltalli, Sarah J Kinston, Dónal O'Carroll, Kamil R Kranc, Berthold Göttgens","doi":"10.1016/j.stem.2023.12.001","DOIUrl":"10.1016/j.stem.2023.12.001","url":null,"abstract":"<p><p>The paradigmatic hematopoietic tree model is increasingly recognized to be limited, as it is based on heterogeneous populations largely defined by non-homeostatic assays testing cell fate potentials. Here, we combine persistent labeling with time-series single-cell RNA sequencing to build a real-time, quantitative model of in vivo tissue dynamics for murine bone marrow hematopoiesis. We couple cascading single-cell expression patterns with dynamic changes in differentiation and growth speeds. The resulting explicit linkage between molecular states and cellular behavior reveals widely varying self-renewal and differentiation properties across distinct lineages. Transplanted stem cells show strong acceleration of differentiation at specific stages of erythroid and neutrophil production, illustrating how the model can quantify the impact of perturbations. Our reconstruction of dynamic behavior from snapshot measurements is akin to how a kinetoscope allows sequential images to merge into a movie. We posit that this approach is generally applicable to understanding tissue-scale dynamics at high resolution.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"244-259.e10"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139111392","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 : 2024-01-04DOI: 10.1016/j.stem.2023.12.006
Joep Beumer, Hans Clevers
{"title":"Hallmarks of stemness in mammalian tissues.","authors":"Joep Beumer, Hans Clevers","doi":"10.1016/j.stem.2023.12.006","DOIUrl":"10.1016/j.stem.2023.12.006","url":null,"abstract":"<p><p>All adult tissues experience wear and tear. Most tissues can compensate for cell loss through the activity of resident stem cells. Although the cellular maintenance strategies vary greatly between different adult (read: postnatal) tissues, the function of stem cells is best defined by their capacity to replace lost tissue through division. We discuss a set of six complementary hallmarks that are key enabling features of this basic function. These include longevity and self-renewal, multipotency, transplantability, plasticity, dependence on niche signals, and maintenance of genome integrity. We discuss these hallmarks in the context of some of the best-understood adult stem cell niches.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"31 1","pages":"7-24"},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10769195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139107008","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 : 2024-01-04DOI: 10.1016/j.stem.2023.12.010
Shree Bose, Xiling Shen
{"title":"The KRAS tour: Studying metabolic reprogramming in isogenic pancreatic cancer organoids.","authors":"Shree Bose, Xiling Shen","doi":"10.1016/j.stem.2023.12.010","DOIUrl":"10.1016/j.stem.2023.12.010","url":null,"abstract":"<p><p>Using an isogenic organoid platform to model pancreatic cancer, Duan et al. establish an important link between mutant KRAS and cholesterol metabolism and identify perhexiline maleate as a possible therapeutic to target this relationship.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"31 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139107009","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 : 2023-12-07Epub Date: 2023-10-27DOI: 10.1016/j.stem.2023.09.014
Yusheng Cai, Muzhao Xiong, Zijuan Xin, Chengyu Liu, Jie Ren, Xiying Yang, Jinghui Lei, Wei Li, Feifei Liu, Qun Chu, Yiyuan Zhang, Jian Yin, Yanxia Ye, Dingyi Liu, Yanling Fan, Shuhui Sun, Yaobin Jing, Qian Zhao, Liyun Zhao, Shanshan Che, Yandong Zheng, Haoteng Yan, Shuai Ma, Si Wang, Juan Carlos Izpisua Belmonte, Jing Qu, Weiqi Zhang, Guang-Hui Liu
{"title":"Decoding aging-dependent regenerative decline across tissues at single-cell resolution.","authors":"Yusheng Cai, Muzhao Xiong, Zijuan Xin, Chengyu Liu, Jie Ren, Xiying Yang, Jinghui Lei, Wei Li, Feifei Liu, Qun Chu, Yiyuan Zhang, Jian Yin, Yanxia Ye, Dingyi Liu, Yanling Fan, Shuhui Sun, Yaobin Jing, Qian Zhao, Liyun Zhao, Shanshan Che, Yandong Zheng, Haoteng Yan, Shuai Ma, Si Wang, Juan Carlos Izpisua Belmonte, Jing Qu, Weiqi Zhang, Guang-Hui Liu","doi":"10.1016/j.stem.2023.09.014","DOIUrl":"10.1016/j.stem.2023.09.014","url":null,"abstract":"<p><p>Regeneration across tissues and organs exhibits significant variation throughout the body and undergoes a progressive decline with age. To decode the relationships between aging and regenerative capacity, we conducted a comprehensive single-cell transcriptome analysis of regeneration in eight tissues from young and aged mice. We employed diverse analytical models to study tissue regeneration and unveiled the intricate cellular and molecular mechanisms underlying the attenuated regenerative processes observed in aged tissues. Specifically, we identified compromised stem cell mobility and inadequate angiogenesis as prominent contributors to this age-associated decline in regenerative capacity. Moreover, we discovered a unique subset of Arg1<sup>+</sup> macrophages that were activated in young tissues but suppressed in aged regenerating tissues, suggesting their important role in age-related immune response disparities during regeneration. This study provides a comprehensive single-cell resource for identifying potential targets for interventions aimed at enhancing regenerative outcomes in the aging population.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1674-1691.e8"},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66784770","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 : 2023-12-07Epub Date: 2023-11-28DOI: 10.1016/j.stem.2023.10.008
Fatima Rizvi, Yu-Ri Lee, Ricardo Diaz-Aragon, Pushpinder S Bawa, Juhoon So, Rodrigo M Florentino, Susan Wu, Arianna Sarjoo, Emily Truong, Anna R Smith, Feiya Wang, Elissa Everton, Alina Ostrowska, Kyounghwa Jung, Ying Tam, Hiromi Muramatsu, Norbert Pardi, Drew Weissman, Alejandro Soto-Gutierrez, Donghun Shin, Valerie Gouon-Evans
{"title":"VEGFA mRNA-LNP promotes biliary epithelial cell-to-hepatocyte conversion in acute and chronic liver diseases and reverses steatosis and fibrosis.","authors":"Fatima Rizvi, Yu-Ri Lee, Ricardo Diaz-Aragon, Pushpinder S Bawa, Juhoon So, Rodrigo M Florentino, Susan Wu, Arianna Sarjoo, Emily Truong, Anna R Smith, Feiya Wang, Elissa Everton, Alina Ostrowska, Kyounghwa Jung, Ying Tam, Hiromi Muramatsu, Norbert Pardi, Drew Weissman, Alejandro Soto-Gutierrez, Donghun Shin, Valerie Gouon-Evans","doi":"10.1016/j.stem.2023.10.008","DOIUrl":"10.1016/j.stem.2023.10.008","url":null,"abstract":"<p><p>The liver is known for its remarkable regenerative ability through proliferation of hepatocytes. Yet, during chronic injury or severe hepatocyte death, proliferation of hepatocytes is exhausted. To overcome this hurdle, we propose vascular-endothelial-growth-factor A (VEGFA) as a therapeutic means to accelerate biliary epithelial-cell (BEC)-to-hepatocyte conversion. Investigation in zebrafish establishes that blocking VEGF receptors abrogates BEC-driven liver repair, while VEGFA overexpression promotes it. Delivery of VEGFA via nonintegrative and safe nucleoside-modified mRNA encapsulated into lipid nanoparticles (mRNA-LNPs) in acutely or chronically injured mouse livers induces robust BEC-to-hepatocyte conversion and elimination of steatosis and fibrosis. In human and murine diseased livers, we further identified VEGFA-receptor KDR-expressing BECs associated with KDR-expressing cell-derived hepatocytes. This work defines KDR-expressing cells, most likely being BECs, as facultative progenitors. This study reveals unexpected therapeutic benefits of VEGFA delivered via nucleoside-modified mRNA-LNP, whose safety is widely validated with COVID-19 vaccines, for harnessing BEC-driven repair to potentially treat liver diseases.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1640-1657.e8"},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465042","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 : 2023-12-07Epub Date: 2023-10-18DOI: 10.1016/j.stem.2023.09.010
Amy L Wilkinson, Irene Zorzan, Peter J Rugg-Gunn
{"title":"Epigenetic regulation of early human embryo development.","authors":"Amy L Wilkinson, Irene Zorzan, Peter J Rugg-Gunn","doi":"10.1016/j.stem.2023.09.010","DOIUrl":"10.1016/j.stem.2023.09.010","url":null,"abstract":"<p><p>Studies of mammalian development have advanced our understanding of the genetic, epigenetic, and cellular processes that orchestrate embryogenesis and have uncovered new insights into the unique aspects of human embryogenesis. Recent studies have now produced the first epigenetic maps of early human embryogenesis, stimulating new ideas about epigenetic reprogramming, cell fate control, and the potential mechanisms underpinning developmental plasticity in human embryos. In this review, we discuss these new insights into the epigenetic regulation of early human development and the importance of these processes for safeguarding development. We also highlight unanswered questions and key challenges that remain to be addressed.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1569-1584"},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686266","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 : 2023-11-02Epub Date: 2023-10-12DOI: 10.1016/j.stem.2023.09.008
Lucca L M Derks, Ruben van Boxtel
{"title":"Stem cell mutations, associated cancer risk, and consequences for regenerative medicine.","authors":"Lucca L M Derks, Ruben van Boxtel","doi":"10.1016/j.stem.2023.09.008","DOIUrl":"10.1016/j.stem.2023.09.008","url":null,"abstract":"<p><p>Mutation accumulation in stem cells has been associated with cancer risk. However, the presence of numerous mutant clones in healthy tissues has raised the question of what limits cancer initiation. Here, we review recent developments in characterizing mutation accumulation in healthy tissues and compare mutation rates in stem cells during development and adult life with corresponding cancer risk. A certain level of mutagenesis within the stem cell pool might be beneficial to limit the size of malignant clones through competition. This knowledge impacts our understanding of carcinogenesis with potential consequences for the use of stem cells in regenerative medicine.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1421-1433"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41223578","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 : 2023-11-02Epub Date: 2023-10-20DOI: 10.1016/j.stem.2023.09.015
Lei Chen, Xia Qiu, Abigail Dupre, Oscar Pellon-Cardenas, Xiaojiao Fan, Xiaoting Xu, Prateeksha Rout, Katherine D Walton, Joseph Burclaff, Ruolan Zhang, Wenxin Fang, Rachel Ofer, Alexandra Logerfo, Kiranmayi Vemuri, Sheila Bandyopadhyay, Jianming Wang, Gaetan Barbet, Yan Wang, Nan Gao, Ansu O Perekatt, Wenwei Hu, Scott T Magness, Jason R Spence, Michael P Verzi
{"title":"TGFB1 induces fetal reprogramming and enhances intestinal regeneration.","authors":"Lei Chen, Xia Qiu, Abigail Dupre, Oscar Pellon-Cardenas, Xiaojiao Fan, Xiaoting Xu, Prateeksha Rout, Katherine D Walton, Joseph Burclaff, Ruolan Zhang, Wenxin Fang, Rachel Ofer, Alexandra Logerfo, Kiranmayi Vemuri, Sheila Bandyopadhyay, Jianming Wang, Gaetan Barbet, Yan Wang, Nan Gao, Ansu O Perekatt, Wenwei Hu, Scott T Magness, Jason R Spence, Michael P Verzi","doi":"10.1016/j.stem.2023.09.015","DOIUrl":"10.1016/j.stem.2023.09.015","url":null,"abstract":"<p><p>The gut epithelium has a remarkable ability to recover from damage. We employed a combination of high-throughput sequencing approaches, mouse genetics, and murine and human organoids and identified a role for TGFB signaling during intestinal regeneration following injury. At 2 days following irradiation (IR)-induced damage of intestinal crypts, a surge in TGFB1 expression is mediated by monocyte/macrophage cells at the location of damage. The depletion of macrophages or genetic disruption of TGFB signaling significantly impaired the regenerative response. Intestinal regeneration is characterized by the induction of a fetal-like transcriptional signature during repair. In organoid culture, TGFB1 treatment was necessary and sufficient to induce the fetal-like/regenerative state. Mesenchymal cells were also responsive to TGFB1 and enhanced the regenerative response. Mechanistically, pro-regenerative factors, YAP/TEAD and SOX9, are activated in the epithelium exposed to TGFB1. Finally, pre-treatment with TGFB1 enhanced the ability of primary epithelial cultures to engraft into damaged murine colon, suggesting promise for cellular therapy.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"1520-1537.e8"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686270","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}