Abstract
Centromere protein A (CENP-A) is a homolog of histone H3 that epigenetically marks the heterochromatin of chromosomes. CENP-A is 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 and cardiac progenitor cells (CPCs) has not been previously studied. This study shows that CENP-A is expressed in CPCs and declines with age. Silencing CENP-A results in a decreased CPC growth rate, reduced cell number in phase G2/M of the cell cycle, and increased senescence-associated β-galactosidase activity. Lineage commitment is not affected by CENP-A silencing, suggesting that cell cycle arrest induced by loss of CENP-A is a consequence of senescence and not differentiation. CENP-A knockdown does not exacerbate cell death in undifferentiated CPCs, but increases apoptosis upon lineage commitment. Taken together, these results indicate that CPCs maintain relatively high levels of CENP-A early in life, which is necessary for sustaining proliferation, inhibiting senescence, and promoting survival following differentiation of CPCs.
Original language | English (US) |
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Pages (from-to) | 739-748 |
Number of pages | 10 |
Journal | Cell Cycle |
Volume | 13 |
Issue number | 5 |
DOIs | |
State | Published - Mar 1 2014 |
Externally published | Yes |
Keywords
- Cardiac progenitor cell
- Cell cycle
- CENP-A
- Heart
- Senescence
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology