Department of Pediatrics (B.N.S., M.K., B.M.O.), University of Minnesota.
Department of Biomedical Engineering (B.N.S., E.G.T., B.M.O.), University of Minnesota.
Circ Res. 2023 Feb 17;132(4):519-540. doi: 10.1161/CIRCRESAHA.122.321770. Epub 2023 Feb 16.
During cardiac development and morphogenesis, cardiac progenitor cells differentiate into cardiomyocytes that expand in number and size to generate the fully formed heart. Much is known about the factors that regulate initial differentiation of cardiomyocytes, and there is ongoing research to identify how these fetal and immature cardiomyocytes develop into fully functioning, mature cells. Accumulating evidence indicates that maturation limits proliferation and conversely proliferation occurs rarely in cardiomyocytes of the adult myocardium. We term this oppositional interplay the proliferation-maturation dichotomy. Here we review the factors that are involved in this interplay and discuss how a better understanding of the proliferation-maturation dichotomy could advance the utility of human induced pluripotent stem cell-derived cardiomyocytes for modeling in 3-dimensional engineered cardiac tissues to obtain truly adult-level function.
在心脏发育和形态发生过程中，心脏祖细胞分化为心肌细胞，数量和大小增加，从而生成完全形成的心脏。人们已经了解了许多调节心肌细胞初始分化的因素，并且正在进行研究以确定这些胎儿和未成熟的心肌细胞如何发育成功能完全成熟的细胞。越来越多的证据表明，成熟会限制增殖，相反，在成年心肌细胞中，增殖很少发生。我们将这种相反的相互作用称为增殖-成熟二分法。在这里，我们回顾了参与这种相互作用的因素，并讨论了更好地理解增殖-成熟二分法如何能够提高人类诱导多能干细胞衍生的心肌细胞在 3 维工程心脏组织中建模的实用性，以获得真正的成人水平的功能。
