title: CENP-A is essential for cardiac progenitor cell proliferation.
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.
authors.affiliation: San Diego Heart Research Institute and the Department of Biology; San Diego State University; San Diego, CA USA.
authors.forename: Michael
authors.initials: M
authors.lastname: McGregor
authors.affiliation: San Diego Heart Research Institute and the Department of Biology; San Diego State University; San Diego, CA USA.
authors.forename: Nirmala
authors.initials: N
authors.lastname: Hariharan
authors.affiliation: San Diego Heart Research Institute and the Department of Biology; San Diego State University; San Diego, CA USA.
authors.forename: Anya Y
authors.initials: AY
authors.lastname: Joyo
authors.affiliation: Sanford-Burnham Medical Research Institute; La Jolla, CA USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Margolis
authors.affiliation: San Diego Heart Research Institute and the Department of Biology; San Diego State University; San Diego, CA USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sussman
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D001324:Autoantigens; C000619701:Cenpa protein, mouse; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone
keywords: CENP-A; cardiac progenitor cell; cell cycle; heart; senescence