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Cell. 2015 Jan 15;160(1-2):285-98. doi: 10.1016/j.cell.2014.12.002.

Identification and specification of the mouse skeletal stem cell.

Author information

1
Department of Surgery, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA. Electronic address: chazchan@stanford.edu.
2
Department of Surgery, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
3
Departments of Pathology and Developmental Biology, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
4
Departments of Pathology and Developmental Biology, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
5
Department of Surgery, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
6
Stanford Cancer Institute, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
7
Departments of Pathology and Developmental Biology, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA; Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
8
Department of Surgery, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA. Electronic address: longaker@stanford.edu.

Abstract

How are skeletal tissues derived from skeletal stem cells? Here, we map bone, cartilage, and stromal development from a population of highly pure, postnatal skeletal stem cells (mouse skeletal stem cells, mSSCs) to their downstream progenitors of bone, cartilage, and stromal tissue. We then investigated the transcriptome of the stem/progenitor cells for unique gene-expression patterns that would indicate potential regulators of mSSC lineage commitment. We demonstrate that mSSC niche factors can be potent inducers of osteogenesis, and several specific combinations of recombinant mSSC niche factors can activate mSSC genetic programs in situ, even in nonskeletal tissues, resulting in de novo formation of cartilage or bone and bone marrow stroma. Inducing mSSC formation with soluble factors and subsequently regulating the mSSC niche to specify its differentiation toward bone, cartilage, or stromal cells could represent a paradigm shift in the therapeutic regeneration of skeletal tissues.

PMID:
25594184
PMCID:
PMC4297645
DOI:
10.1016/j.cell.2014.12.002
[Indexed for MEDLINE]
Free PMC Article

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