Transcriptional Regulation of Postnatal Cardiomyocyte Maturation and Regeneration

Abstract

During the postnatal period, mammalian cardiomyocytes undergo numerous maturational changes associated with increased cardiac function and output, including hypertrophic growth, cell cycle exit, sarcomeric protein isoform switching, and mitochondrial maturation. These changes come at the expense of loss of regenerative capacity of the heart, contributing to heart failure after cardiac injury in adults. While most studies focus on the transcriptional regulation of embryonic or adult cardiomyocytes, the transcriptional changes that occur during the postnatal period are relatively unknown. In this review, we focus on the transcriptional regulators responsible for these aspects of cardiomyocyte maturation during the postnatal period in mammals. By specifically highlighting this transitional period, we draw attention to critical processes in cardiomyocyte maturation with potential therapeutic implications in cardiovascular disease.

Three-dimensional cardiac organoid formation accelerates the functional maturation of human induced pluripotent stem cell-derived cardiomyocytes

“…Therefore, we analyzed the isoform switching in 2D-CMs and 3D hiCOs based on the gene expression level of cardiac myofibril assembly-related isoforms, which are a sign of sarcomere maturation. In the developing heart, the predominant isoform of myosin heavy chain (MHC) protein switches from β-MHC (MYH7) to α-MHC (MYH6) [25][26][27][28], and mature CMs express a higher level of cardiac troponin I3 (TNNI3) than fetal cardiac troponin I1 (TNNI1) [25,[29][30][31][32][33][34][35].…”

Foxm1 drives cardiomyocyte proliferation in adult zebrafish after cardiac injury

“…Loosely organized myofibrils are produced in embryonic cardiomyocytes at the beginning of sarcomere assembly, but a large expansion in myofibril number occurs during cell maturation coupled with increased organization of the sarcomere into banded, contractile structures of the Z-line and M-line [10][11][12]. In addition to this, mouse embryonic cardiomyocytes produce sarcomere components such as Myh7, Myl7, and Tnni1 while adult cells predominantly express Myh6, Myl2, and Tnni3 after maturation [11][12][13][14][15][16][17]. With increased contractile organization, adult cardiomyocytes also require higher levels of ATP to sustain cardiac function.…”

“…These processes include changes in sarcomere assembly, metabolism, and cell cycle activity. Loosely organized myofibrils are produced in embryonic cardiomyocytes at the beginning of sarcomere assembly, but a large expansion in myofibril number occurs during cell maturation coupled with increased organization of the sarcomere into banded, contractile structures of the Z-line and M-line [10-12]. In addition to this, mouse embryonic cardiomyocytes produce sarcomere components such as Myh7, Myl7 , and Tnni1 while adult cells predominantly express Myh6, Myl2 , and Tnni3 after maturation [11-17].…”

“…Unlike mammals, adult zebrafish cardiomyocytes can dedifferentiate from a mature to an embryonic state and exhibit robust proliferation under different injury conditions [4-6, 12, 29]. This makes them an ideal model to study which genes regulate the proliferative switch in these cells.…”

Child’s heart development and contractility from prenatal to postnatal period

“…Существенный вклад в понимание проблемы становления контрактильности детского сердца [1,2] вносят современные знания о морфологических проявлениях продолжающегося в постэмбриональном периоде кардиального миогенеза [3,4], об ультраструктурных изменениях в постнатальный период не завершившего морфогенез миокарда [5,6] с точки зрения соотношения процессов гистогенеза -пролиферации, дифференцировки, миграции и клеточной гибели, последовательное протекание которых приводит к формированию миокарда в норме [7].…”