| Literature DB >> 30241615 |
Charles K F Chan1, Gunsagar S Gulati2, Rahul Sinha3, Justin Vincent Tompkins4, Michael Lopez4, Ava C Carter5, Ryan C Ransom2, Andreas Reinisch3, Taylor Wearda4, Matthew Murphy4, Rachel E Brewer4, Lauren S Koepke4, Owen Marecic4, Anoop Manjunath2, Eun Young Seo4, Tripp Leavitt4, Wan-Jin Lu3, Allison Nguyen3, Stephanie D Conley3, Ankit Salhotra4, Thomas H Ambrosi4, Mimi R Borrelli4, Taylor Siebel3, Karen Chan3, Katharina Schallmoser6, Jun Seita7, Debashis Sahoo8, Henry Goodnough9, Julius Bishop9, Michael Gardner9, Ravindra Majeti10, Derrick C Wan4, Stuart Goodman9, Irving L Weissman3, Howard Y Chang5, Michael T Longaker11.
Abstract
Stem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individual hSSCs reveals overall similarity between hSSCs obtained from different sources and partially explains skewed differentiation toward cartilage in fetal and iPSC-derived hSSCs. hSSCs undergo local expansion in response to acute skeletal injury. In addition, hSSC-derived stroma can maintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions. Finally, we combine gene expression and epigenetic data of mouse skeletal stem cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent pathways driving SSC-mediated skeletogenesis. VIDEO ABSTRACT. Published by Elsevier Inc.Entities:
Keywords: ATAC-sequencing; HSC; and stromal progenitor; bone; bone fracture repair; bone marrow niche; cartilage; human skeletal stem cell; single cell RNA-sequencing
Mesh：
Year: 2018 PMID： 30241615 PMCID： PMC6400492 DOI： 10.1016/j.cell.2018.07.029
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582