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Cell Cycle. 2014;13(5):739-48. doi: 10.4161/cc.27549. Epub 2013 Dec 20.

CENP-A is essential for cardiac progenitor cell proliferation.

Author information

1
San Diego Heart Research Institute and the Department of Biology; San Diego State University; San Diego, CA USA.
2
Sanford-Burnham Medical Research Institute; La Jolla, CA USA.

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 G 2/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.

KEYWORDS:

CENP-A; cardiac progenitor cell; cell cycle; heart; senescence

PMID:
24362315
PMCID:
PMC3979910
DOI:
10.4161/cc.27549
[Indexed for MEDLINE]
Free PMC Article

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