CENP-A is essential for cardiac progenitor cell proliferation

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Cell Death / genetics
  • Cell Differentiation
  • Cell Proliferation*
  • Cell Survival / genetics
  • Cells, Cultured
  • Cellular Senescence
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • G2 Phase Cell Cycle Checkpoints
  • Mice
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism*


  • Autoantigens
  • Cenpa protein, mouse
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone