Description
Centromere protein A (CENP-A) is a homologue of histone H3 that epigenetically marks the heterochromatin of chromosomes. CENP-A has been shown to be a critical component of the cell cycle machinery that is necessary for proper assembly of the mitotic spindle. However, the role of CENP-A in the heart has not been previously studied. The objective of this study is to elucidate the role of CENP-A in the context of the heart and cardiac progenitor cells (CPCs). This report shows that CENP-A expression declines in the heart and CPCs with age, correlating with decreased proliferative capacity and increased cellular senescence. Acute knockdown of CENP-A via transcriptional targeting of shRNA results in a decline in CPC growth rate and a reduction of CPCs in G2 phase of the cell cycle. Furthermore, CENP-A knockdown causes increased senescence associated _-galactosidase activity. CENP-A knockdown does not exacerbate cell death in undifferentiated CPCs, but increases apoptosis two fold in dexamethasone differentiated cells. Taken together, these results indicate that CPCs maintain relatively high levels of CENP-A early in life and that this level is necessary for sustaining the proliferative and differentiation capacity of CPCs. Down regulation of CENP-A ablates CPC growth and leads to apoptotic cell death when challenged to differentiate. Therefore, CENP-A is a critical component of the cell cycle in the heart that is necessary for maintaining CPC proliferation.
