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Identification of the Human Skeletal Stem Cell.

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
Cell | 2018

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.

Pubmed ID: 30241615

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIDCR NIH HHS, United States
    Id: R21 DE019274
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR063717
  • Agency: NIA NIH HHS, United States
    Id: K99 AG049958
  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE026730
  • Agency: NIDCR NIH HHS, United States
    Id: R56 DE025597
  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE021683
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL099999
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL099776
  • Agency: NIDCR NIH HHS, United States
    Id: R21 DE024230
  • Agency: NIA NIH HHS, United States
    Id: R00 AG049958
  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE027323
  • Agency: NHGRI NIH HHS, United States
    Id: P50 HG007735
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR055650
  • Agency: NIDCR NIH HHS, United States
    Id: U24 DE026914
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK115600
  • Agency: NCI NIH HHS, United States
    Id: R01 CA086065
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL058770
  • Agency: Howard Hughes Medical Institute, United States

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