RESUMO
Tissue regenerative potential displays striking divergence across phylogeny and ontogeny, but the underlying mechanisms remain enigmatic. Loss of mammalian cardiac regenerative potential correlates with cardiomyocyte cell-cycle arrest and polyploidization as well as the development of postnatal endothermy. We reveal that diploid cardiomyocyte abundance across 41 species conforms to Kleiber's law-the ¾-power law scaling of metabolism with bodyweight-and inversely correlates with standard metabolic rate, body temperature, and serum thyroxine level. Inactivation of thyroid hormone signaling reduces mouse cardiomyocyte polyploidization, delays cell-cycle exit, and retains cardiac regenerative potential in adults. Conversely, exogenous thyroid hormones inhibit zebrafish heart regeneration. Thus, our findings suggest that loss of heart regenerative capacity in adult mammals is triggered by increasing thyroid hormones and may be a trade-off for the acquisition of endothermy.
Assuntos
Coração/fisiologia , Miócitos Cardíacos/fisiologia , Poliploidia , Regeneração/fisiologia , Hormônios Tireóideos/fisiologia , Animais , Regulação da Temperatura Corporal , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Diploide , Camundongos , Miócitos Cardíacos/classificação , Filogenia , Receptores dos Hormônios Tireóideos/genética , Receptores dos Hormônios Tireóideos/fisiologia , Regeneração/efeitos dos fármacos , Regeneração/genética , Transdução de Sinais , Hormônios Tireóideos/farmacologia , Peixe-ZebraRESUMO
The nucleus contains the genetic blueprint of the cell and myriad interactions within this subcellular structure are required for gene regulation. In the current scientific era, characterization of these gene regulatory networks through biochemical techniques coupled with systems-wide 'omic' approaches has become commonplace. However, these strategies are limited because they represent a mere snapshot of the cellular state. To obtain a holistic understanding of nuclear dynamics, relevant molecules must be studied in their native contexts in living systems. Live-cell imaging approaches are capable of providing quantitative assessment of the dynamics of gene regulatory interactions within the nucleus. We survey recent insights into what live-cell imaging approaches have provided the field of nuclear dynamics. In this review, we focus on interactions of DNA with other DNA loci, proteins, RNA, and the nuclear envelope. WIREs Syst Biol Med 2017, 9:e1372. doi: 10.1002/wsbm.1372 For further resources related to this article, please visit the WIREs website.
