CENP-A is essential for cardiac progenitor cell proliferation

Michael McGregor, Nirmala Hariharan, Anya Y. Joyo, Robert L. Margolis, Mark A. Sussman

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 languageEnglish (US)
Pages (from-to)739-748
Number of pages10
JournalCell Cycle
Volume13
Issue number5
DOIs
StatePublished - Mar 1 2014
Externally publishedYes

Keywords

  • Cardiac progenitor cell
  • Cell cycle
  • CENP-A
  • Heart
  • Senescence

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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