title: Identification and specification of the mouse skeletal stem cell.
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.
authors.affiliation: 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.
authors.forename: Charles K F
authors.initials: CK
authors.lastname: Chan
authors.affiliation: 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.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Seo
authors.affiliation: Departments of Pathology and Developmental Biology, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
authors.forename: James Y
authors.initials: JY
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Lo
authors.affiliation: 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.
authors.forename: Adrian
authors.initials: A
authors.lastname: McArdle
authors.affiliation: 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.
authors.forename: Rahul
authors.initials: R
authors.lastname: Sinha
authors.affiliation: 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.
authors.forename: Ruth
authors.initials: R
authors.lastname: Tevlin
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Seita
authors.affiliation: Departments of Pathology and Developmental Biology, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Vincent-Tompkins
authors.affiliation: 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.
authors.forename: Taylor
authors.initials: T
authors.lastname: Wearda
authors.affiliation: 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.
authors.forename: Wan-Jin
authors.initials: WJ
authors.lastname: Lu
authors.affiliation: Department of Surgery, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
authors.forename: Kshemendra
authors.initials: K
authors.lastname: Senarath-Yapa
authors.affiliation: Department of Surgery, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Chung
authors.affiliation: Department of Surgery, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
authors.forename: Owen
authors.initials: O
authors.lastname: Marecic
authors.affiliation: Department of Surgery, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
authors.forename: Misha
authors.initials: M
authors.lastname: Tran
authors.affiliation: Stanford Cancer Institute, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
authors.forename: Kelley S
authors.initials: KS
authors.lastname: Yan
authors.affiliation: Departments of Pathology and Developmental Biology, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
authors.forename: Rosalynd
authors.initials: R
authors.lastname: Upton
authors.affiliation: 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.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Walmsley
authors.affiliation: Departments of Pathology and Developmental Biology, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Debashis
authors.initials: D
authors.lastname: Sahoo
authors.affiliation: Stanford Cancer Institute, Stanford University, 450 Serra Mall, Palo Alto, CA 94305, USA.
authors.forename: Calvin J
authors.initials: CJ
authors.lastname: Kuo
authors.affiliation: 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.
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.affiliation: 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.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology*; D002356:Cartilage / Q000166:cytology; D019070:Cell Lineage; D003433:Crosses, Genetic; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction
chemical_list: D019485:Bone Morphogenetic Proteins