title: In vivo fate mapping identifies mesenchymal progenitor cells.
abstract: Adult mesenchymal progenitor cells have enormous potential for use in regenerative medicine. However, the true identity of the progenitors in vivo and their progeny has not been precisely defined. We hypothesize that cells expressing a smooth muscle α-actin promoter (αSMA)-directed Cre transgene represent mesenchymal progenitors of adult bone tissue. By combining complementary colors in combination with transgenes activating at mature stages of the lineage, we characterized the phenotype and confirmed the ability of isolated αSMA(+) cells to progress from a progenitor to fully mature state. In vivo lineage tracing experiments using a new bone formation model confirmed the osteogenic phenotype of αSMA(+) cells. In vitro analysis of the in vivo-labeled SMA9(+) cells supported their differentiation potential into mesenchymal lineages. Using a fracture-healing model, αSMA9(+) cells served as a pool of fibrocartilage and skeletal progenitors. Confirmation of the transition of αSMA9(+) progenitor cells to mature osteoblasts during fracture healing was assessed by activation of bone-specific Col2.3emd transgene. Our findings provide a novel in vivo identification of defined population of mesenchymal progenitor cells with active role in bone remodeling and regeneration.
authors.affiliation: Department of Physiology and Immunology, School of Medicine, University of Zagreb, Zagreb Croatia.
authors.forename: Danka
authors.initials: D
authors.lastname: Grcevic
authors.forename: Slavica
authors.initials: S
authors.lastname: Pejda
authors.forename: Brya G
authors.initials: BG
authors.lastname: Matthews
authors.forename: Dario
authors.initials: D
authors.lastname: Repic
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kronenberg
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.forename: Peter
authors.initials: P
authors.lastname: Maye
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Adams
authors.forename: David W
authors.initials: DW
authors.lastname: Rowe
authors.forename: Hector L
authors.initials: HL
authors.lastname: Aguila
authors.forename: Ivo
authors.initials: I
authors.lastname: Kalajzic
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D001861:Bone Regeneration; D016723:Bone Remodeling; D002454:Cell Differentiation; D019070:Cell Lineage; D005260:Female; D017102:Fracture Healing; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013977:Tibia / Q000473:pathology
chemical_list: D000199:Actins; D000943:Antigens, Differentiation; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins
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