title: sdf1 Expression reveals a source of perivascular-derived mesenchymal stem cells in zebrafish.
abstract: There is accumulating evidence that mesenchymal stem cells (MSCs) have their origin as perivascular cells (PVCs) in vivo, but precisely identifying them has been a challenge, as they have no single definitive marker and are rare. We have developed a fluorescent transgenic vertebrate model in which PVC can be visualized in vivo based upon sdf1 expression in the zebrafish. Prospective isolation and culture of sdf1(DsRed) PVC demonstrated properties consistent with MSC including prototypical cell surface marker expression; mesodermal differentiation into adipogenic, osteogenic, and chondrogenic lineages; and the ability to support hematopoietic cells. Global proteomic studies performed by two-dimensional liquid chromatography and tandem mass spectrometry revealed a high degree of similarity to human MSC (hMSC) and discovery of novel markers (CD99, CD151, and MYOF) that were previously unknown to be expressed by hMSC. Dynamic in vivo imaging during fin regeneration showed that PVC may arise from undifferentiated mesenchyme providing evidence of a PVC-MSC relationship. This is the first model, established in zebrafish, in which MSC can be visualized in vivo and will allow us to better understand their function in a native environment.
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Troy C
authors.initials: TC
authors.lastname: Lund
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Patrinostro
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Kramer
authors.forename: Paul
authors.initials: P
authors.lastname: Stadem
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Higgins
authors.forename: Todd W
authors.initials: TW
authors.lastname: Markowski
authors.forename: Matt S
authors.initials: MS
authors.lastname: Wroblewski
authors.forename: Diane S
authors.initials: DS
authors.lastname: Lidke
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology; D040901:Proteomics; D012038:Regeneration; D019076:Transgenes; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D054377:Chemokine CXCL12; D029961:Zebrafish Proteins; C579453:cxcl12a protein, zebrafish
keywords: Angiogenesis; Mesenchymal stem cells; Multipotential differentiation; Pericytes; zebrafish