Division of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Nucleus. 2023 Dec;14(1):2246310. doi: 10.1080/19491034.2023.2246310.
In adult mammals, many heart muscle cells (cardiomyocytes) are polyploid, do not proliferate (post-mitotic), and, consequently, cannot contribute to heart regeneration. In contrast, fetal and neonatal heart muscle cells are diploid, proliferate, and contribute to heart regeneration. We have identified interdependent changes of the nuclear lamina, nuclear pore complexes, and DNA-content (ploidy) in heart muscle cell maturation. These results offer new perspectives on how cells alter their nuclear transport and, with that, their gene regulation in response to extracellular signals. We present how changes of the nuclear lamina alter nuclear pore complexes in heart muscle cells. The consequences of these changes for cellular regeneration and stress response in the heart are discussed.
在成年哺乳动物中,许多心肌细胞(cardiomyocytes)是多倍体,不增殖(有丝分裂后),因此不能促进心脏再生。相比之下,胎儿和新生儿的心肌细胞是二倍体,增殖并促进心脏再生。我们已经确定了心肌细胞成熟过程中核层、核孔复合物和 DNA 含量(ploidy)的相互依赖变化。这些结果为细胞如何改变其核运输以及随之改变其基因调控以响应细胞外信号提供了新的视角。我们展示了核层的变化如何改变心肌细胞中的核孔复合物。讨论了这些变化对心脏细胞再生和应激反应的影响。