RESUMO
Maturation is the last step of heart growth that prepares the organ over the lifetime of the mammal for powerful, effective, and sustained pumping. Structural, gene expression, physiological, and functional specialties of cardiomyocytes describe this mechanism as the heart transits from fetus to adult phases. The main cornerstones of maturation of cardiomyocytes are reviewed and primary regulatory mechanisms are summarized to facilitate and organize these cellular activities. During embryonic development, cardiomyocytes proliferate rigorously but leave the cell cycle permanently immediately after the parturition of the child and experience terminal differentiation. The activation of a host of genes specific for the mature heart is correlated with the exit from the cell cycle. Even when exposed to mitogenic stimuli, the bulk of mature cardiomyocytes do not re-join the cell cycle. The reason for this permanent exit from the cell cycle is shown to be linked with stable switching off of the genes of the cell cycle directly involved in the G2/M transition phase and cytokinesis development. Researchers also trying to explain the molecular mechanism involved in stable inhibition of the gene and described structural changes (epigenetic and chromatin) in this mechanism. Substantial developments in the future with advances in the scientific platforms used for cardiomyocyte maturation research will broaden our understanding of this mechanism and result in better maturation of cardiomyocyte-derived pluripotent stem cells and effective treatment approaches for cardiovascular diseases.
Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Humanos , Animais , Gravidez , Feminino , Criança , Miócitos Cardíacos/metabolismo , Diferenciação Celular/fisiologia , Epigênese Genética , Proliferação de Células , Células-Tronco Pluripotentes Induzidas/metabolismo , MamíferosRESUMO
Wnt signaling is an evolutionary cell-to-cell coordination mechanism and it is highly critical for a variety of physiological processes of an organism's body, including stem cell regeneration, proliferation, division, migration, polarity of a cell, determining fate of the cell and specification of neural crest, neural symmetry and morphogenesis. Wnts are extracellular secreted glycol proteins, consisted of a family of 19 human proteins that represent the complex nature of the regulatory structure and physiological efficiency of signaling. Moreover, a Wnt/ß-catenin-dependent pathway and the ß-catenin-independent pathway that is further classified into the Planar Cell Polarity and Wnt/Ca2+ pathways have been established as key signaling nodes downstream of the frizzled (Fz/Fzd) receptor, and these nodes are extensively analyzed at biochemical and molecular levels. Genetic and epigenetic activities that ultimately characterize the pathway and its subsequent responses contribute to Wnt-ß-catenin signaling pathway hypo or hyper-activation and is associated with the variety of human disorders progression most significantly cancers. Recognizing how this mechanism operates is crucial to the advancement of cancer prevention therapies or regenerative medicine methods.
Assuntos
Via de Sinalização Wnt , beta Catenina , Polaridade Celular , Receptores Frizzled/metabolismo , Humanos , beta Catenina/metabolismoRESUMO
The evolution of a two-chambered heart, with an atrium and a ventricle, has improved heart function in both deuterostomes (vertebrates) and some protostomes (invertebrates). Although studies have examined the unique structure and function of these two chambers, molecular comparisons are few and limited to vertebrates. Here, we focus on the two-chambered protostome heart of the mollusks, offering data that may provide a better understanding of heart evolution. Specifically, we asked if the atrium and ventricle differ at the molecular level in the mollusk heart. To do so, we examined two very different species, the giant African land snail (Lissachatina fulica) and the relatively small, aquatic yesso scallop (Mizuhopecten yessoensis), with the assumption that if they exhibited commonality these similarities would likely reflect those across the phylum. We found that, although the hearts of these two species differed histologically, their cardiac gene function enrichments were similar, as revealed by transcriptomic analysis. Furthermore, the atrium and ventricle in each species had distinct gene function clusters, suggesting an evolutionary differentiation of cardiac chambers in mollusks. Finally, to explore the relationship between vertebrate and invertebrate two-chambered hearts, we compared our transcriptomic data with published data from the zebrafish, a well-studied vertebrate model with a two-chambered heart. Our analysis indicated a functional similarity of ventricular genes between the mollusks and the zebrafish, suggesting that the ventricle was differentiated to achieve the same functions in invertebrates and vertebrates. As the first such study on protostomes, our findings offered initial insights into how the two-chambered heart arose, including a possible understanding of its occurrence in both protostomes and deuterostomes. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00202-0.