Identification of the Human Skeletal Stem Cell.

Journal: 
Cell
Publication Year: 
2018
Authors: 
Charles K F Chan
Gunsagar S Gulati
Rahul Sinha
Justin Vincent Tompkins
Michael Lopez
Ava C Carter
Ryan C Ransom
Andreas Reinisch
Taylor Wearda
Matthew Murphy
Rachel E Brewer
Lauren S Koepke
Owen Marecic
Anoop Manjunath
Eun Young Seo
Tripp Leavitt
Wan-Jin Lu
Allison Nguyen
Stephanie D Conley
Ankit Salhotra
Thomas H Ambrosi
Mimi R Borrelli
Taylor Siebel
Karen Chan
Katharina Schallmoser
Jun Seita
Debashis Sahoo
Henry Goodnough
Julius Bishop
Michael Gardner
Ravindra Majeti
Derrick C Wan
Stuart Goodman
Irving L Weissman
Howard Y Chang
Michael T Longaker
PubMed link: 
30241615
Public Summary: 
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 towards 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.
Scientific 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.