Paradis Alexandra N, Gay Maresha S, Zhang Lubo
Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Drug Discov Today. 2014 May;19(5):602-9. doi: 10.1016/j.drudis.2013.10.019. Epub 2013 Oct 31.
Cardiomyocytes possess a unique ability to transition from mononucleate to the mature binucleate phenotype in late fetal development and around birth. Mononucleate cells are proliferative, whereas binucleate cells exit the cell cycle and no longer proliferate. This crucial period of terminal differentiation dictates cardiomyocyte endowment for life. Adverse early life events can influence development of the heart, affecting cardiomyocyte number and contributing to heart disease late in life. Although much is still unknown about the mechanisms underlying the binucleation process, many studies are focused on molecules involved in cell cycle regulation and cytokinesis as well as epigenetic modifications that can occur during this transition. Better understanding of these mechanisms could provide a basis for recovering the proliferative capacity of cardiomyocytes.
心肌细胞具有独特的能力,在胎儿发育后期和出生前后从单核转变为成熟的双核表型。单核细胞具有增殖能力,而双核细胞退出细胞周期,不再增殖。这个关键的终末分化时期决定了心肌细胞的终身数量。早期不良生活事件会影响心脏发育,影响心肌细胞数量,并导致晚年心脏病。尽管关于双核化过程的潜在机制仍有许多未知之处,但许多研究集中在参与细胞周期调控和胞质分裂的分子以及在此转变过程中可能发生的表观遗传修饰上。更好地理解这些机制可为恢复心肌细胞的增殖能力提供基础。