Heterogeneity in SDF-1 expression defines the vasculogenic potential of adult cardiac progenitor cells
| Autor: | Nicholas F. Tsinoremas, Nanette H. Bishopric, Claudia O. Rodrigues, Ines Chopra, Lina A. Shehadeh, Michael Hoosien, Valerie Otero |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Anatomy and Physiology
Stromal cell Heart Ventricles Cellular differentiation Population Gene Expression lcsh:Medicine 030204 cardiovascular system & hematology Biology Cardiovascular System Cell Growth Mice 03 medical and health sciences 0302 clinical medicine Molecular Cell Biology Animals Progenitor cell education lcsh:Science Cell Shape 030304 developmental biology Tube formation 0303 health sciences Matrigel education.field_of_study Multidisciplinary Multipotent Stem Cells Stem Cells lcsh:R Endothelial Cells Cell Differentiation Chemokine CXCL12 Clone Cells Cell biology Adult Stem Cells Multipotent Stem Cell Immunology Blood Vessels Medicine lcsh:Q Cellular Types Stem cell Myoblasts Cardiac Cell Division Research Article Developmental Biology |
| Zdroj: | PLoS ONE, Vol 6, Iss 8, p e24013 (2011) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Rationale 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. Methods and 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. |
| Databáze: | OpenAIRE |
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