Dissecting the Molecular Relationship Among Various Cardiogenic Progenitor Cells
Rationale: Multiple progenitors derived from the heart and bone marrow have been utilized for cardiac repair. Despite this, not much is known about the molecular identity and relationship among these progenitors. To develop a robust stem cell therapy for the heart, it is critical to understand the molecular identity of the multiple 'cardiogenic progenitor cells' (CPCs).
Objective: This study is the first report of high throughput transcriptional profiling of CPCs carried out on an identical platform.
Methods and Results: Microarray based transcriptional profiling was carried out for three cardiac (ckit+, Sca1+, side population) and two bone marrow (ckit+, mesenchymal stem cell) progenitors, obtained from age- and sex-matched wild type C57BL/6 mice. Analysis indicated that cardiac-derived ckit+ population was very distinct from Sca1+ and SP cells in the downregulation of genes encoding for cell-cell and matrix adhesion proteins, and in the upregulation of developmental genes. Significant enrichment of transcripts involved in DNA replication and repair was observed in bone marrow (BM)-derived progenitors. The BM ckit+ cells appeared to have the least correlation with the other progenitors, with enrichment of immature neutrophil specific molecules.
Conclusions: Our study indicates that cardiac ckit+ cells represent the most primitive population in the rodent heart. Primitive cells of cardiac versus BM origin differ significantly with respect to stemness and cardiac lineage-specific genes, and molecules involved in DNA replication and repair. The detailed molecular profile of progenitors reported here will serve as a useful reference to determine the molecular identity of progenitors used in future preclinical and clinical studies.
- bone marrow cells
- cardiovascular diseases
- stem cell
- cardiac progenitor cells
- Received December 15, 2012.
- Revision received March 4, 2013.
- Accepted March 5, 2013.