title: Identification and characterization of an injury-induced skeletal progenitor.
abstract: The postnatal skeleton undergoes growth, remodeling, and repair. We hypothesized that skeletal progenitor cells active during these disparate phases are genetically and phenotypically distinct. We identified a highly potent regenerative cell type that we term the fracture-induced bone, cartilage, stromal progenitor (f-BCSP) in the fracture callus of adult mice. The f-BCSP possesses significantly enhanced skeletogenic potential compared with BCSPs harvested from uninjured bone. It also recapitulates many gene expression patterns involved in perinatal skeletogenesis. Our results indicate that the skeletal progenitor population is functionally stratified, containing distinct subsets responsible for growth, regeneration, and repair. Furthermore, our findings suggest that injury-induced changes to the skeletal stem and progenitor microenvironments could activate these cells and enhance their regenerative potential.
authors.affiliation: Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305-5148; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Owen
authors.initials: O
authors.lastname: Marecic
authors.affiliation: Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305-5148; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Ruth
authors.initials: R
authors.lastname: Tevlin
authors.affiliation: Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305-5148; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Adrian
authors.initials: A
authors.lastname: McArdle
authors.affiliation: Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305-5148; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Seo
authors.affiliation: Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305-5148; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Taylor
authors.initials: T
authors.lastname: Wearda
authors.affiliation: Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305-5148;
authors.forename: Christopher
authors.initials: C
authors.lastname: Duldulao
authors.affiliation: Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305-5148; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Graham G
authors.identifier: http://orcid.org/0000-0002-9706-8356
authors.initials: GG
authors.lastname: Walmsley
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Allison
authors.initials: A
authors.lastname: Nguyen
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305 chazchan@stanford.edu irv@stanford.edu longaker@stanford.edu.
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305 chazchan@stanford.edu irv@stanford.edu longaker@stanford.edu.
authors.forename: Charles K F
authors.initials: CK
authors.lastname: Chan
authors.affiliation: Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305-5148; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305 chazchan@stanford.edu irv@stanford.edu longaker@stanford.edu.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001846:Bone Development; D001842:Bone and Bones / Q000473:pathology*; D002146:Bony Callus / Q000166:cytology; D002356:Cartilage / Q000473:pathology; D049109:Cell Proliferation; D002469:Cell Separation; D005269:Femur / Q000473:pathology; D050723:Fractures, Bone / Q000473:pathology*; D020869:Gene Expression Profiling; D006614:Hindlimb / Q000528:radiation effects; D039503:Integrin alpha6 / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D010012:Osteogenesis; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology*; D017154:Stromal Cells / Q000166:cytology
chemical_list: D039503:Integrin alpha6
keywords: fracture healing; injury activation; osteogenesis; regeneration; skeletal stem/progenitor cell