title: Heterogeneity in SDF-1 expression defines the vasculogenic potential of adult cardiac progenitor cells.
abstract: BACKGROUND
  The adult myocardium has been reported to harbor several classes of multipotent progenitor cells (CPCs) with tri-lineage differentiation potential. It is not clear whether c-kit+CPCs represent a uniform precursor population or a more complex mixture of cell types.
  
  
  OBJECTIVE
  To characterize and understand vasculogenic heterogeneity within c-kit+presumptive cardiac progenitor cell populations.
  
  
  RESULTS
  c-kit+, sca-1+ CPCs obtained from adult mouse left ventricle expressed stem cell-associated genes, including Oct-4 and Myc, and were self-renewing, pluripotent and clonogenic. Detailed single cell clonal analysis of 17 clones revealed that most (14/17) exhibited trilineage differentiation potential. However, striking morphological differences were observed among clones that were heritable and stable in long-term culture. 3 major groups were identified: round (7/17), flat or spindle-shaped (5/17) and stellate (5/17). Stellate morphology was predictive of vasculogenic differentiation in Matrigel. Genome-wide expression studies and bioinformatic analysis revealed clonally stable, heritable differences in stromal cell-derived factor-1 (SDF-1) expression that correlated strongly with stellate morphology and vasculogenic capacity. Endogenous SDF-1 production contributed directly to vasculogenic differentiation: both shRNA-mediated knockdown of SDF-1 and AMD3100, an antagonist of the SDF-1 receptor CXC chemokine Receptor-4 (CXCR4), reduced tube-forming capacity, while exogenous SDF-1 induced tube formation by 2 non-vasculogenic clones. CPCs producing SDF-1 were able to vascularize Matrigel dermal implants in vivo, while CPCs with low SDF-1 production were not.
  
  
  CONCLUSIONS
  Clonogenic c-kit+, sca-1+ CPCs are heterogeneous in morphology, gene expression patterns and differentiation potential. Clone-specific levels of SDF-1 expression both predict and promote development of a vasculogenic phenotype via a previously unreported autocrine mechanism.
authors: Department of Molecular and Cellular Pharmacology, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, United States of America.
authors: Claudia O
authors: CO
authors: Rodrigues
authors: Lina A
authors: LA
authors: Shehadeh
authors: Michael
authors: M
authors: Hoosien
authors: Valerie
authors: V
authors: Otero
authors: Ines
authors: I
authors: Chopra
authors: Nicholas F
authors: NF
authors: Tsinoremas
authors: Nanette H
authors: NH
authors: Bishopric
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000737:chemistry* / Q000166:cytology*; D002454:Cell Differentiation; D048430:Cell Shape; D054377:Chemokine CXCL12 / Q000032:analysis*; D002999:Clone Cells / Q000737:chemistry / Q000166:cytology; D006352:Heart Ventricles / Q000166:cytology; D051379:Mice; D039902:Multipotent Stem Cells; D032386:Myoblasts, Cardiac / Q000737:chemistry* / Q000166:cytology; D013234:Stem Cells
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse