Format

Send to

Choose Destination
Cell. 2018 Sep 20;175(1):43-56.e21. doi: 10.1016/j.cell.2018.07.029.

Identification of the Human Skeletal Stem Cell.

Author information

1
Department of Surgery, Stanford Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford Medicine, Stanford, CA 94305, USA. Electronic address: chazchan@stanford.edu.
2
Department of Surgery, Stanford Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford Medicine, Stanford, CA 94305, USA.
3
Institute for Stem Cell Biology and Regenerative Medicine, Stanford Medicine, Stanford, CA 94305, USA.
4
Department of Surgery, Stanford Medicine, Stanford, CA 94305, USA.
5
Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
6
Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz, 8036 Graz, Austria.
7
Medical Sciences Innovation Hub Program, RIKEN, Tokyo 103-0027, Japan.
8
Departments of Pediatrics and Computer Science and Engineering, University of California San Diego, San Diego, CA 92093, USA.
9
Department of Orthopedic Surgery, Stanford Medicine, Stanford, CA 94305, USA.
10
Department of Medicine, Division of Hematology, Stanford Medicine, Stanford, CA 94305, USA.
11
Department of Surgery, Stanford Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford Medicine, Stanford, CA 94305, USA. Electronic address: longaker@stanford.edu.

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.

KEYWORDS:

ATAC-sequencing; HSC; and stromal progenitor; bone; bone fracture repair; bone marrow niche; cartilage; human skeletal stem cell; single cell RNA-sequencing

PMID:
30241615
DOI:
10.1016/j.cell.2018.07.029

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center