The negative regulation of gene expression by microRNAs as key driver of inducers and repressors of cardiomyocyte differentiation
Open Access
- 18 August 2022
- journal article
- review article
- Published by Portland Press Ltd. in Clinical Science
- Vol. 136 (16), 1179-1203
- https://doi.org/10.1042/cs20220391
Abstract
Cardiac muscle damage-induced loss of cardiomyocytes (CMs) and dysfunction of the remaining ones leads to heart failure, which nowadays is the number one killer worldwide. Therapies fostering effective cardiac regeneration are the holy grail of cardiovascular research to stop the heart failure epidemic. The main goal of most myocardial regeneration protocols is the generation of new functional CMs through the differentiation of endogenous or exogenous cardiomyogenic cells. Understanding the cellular and molecular basis of cardiomyocyte commitment, specification, differentiation and maturation is needed to devise innovative approaches to replace the CMs lost after injury in the adult heart. The transcriptional regulation of CM differentiation is a highly conserved process that require sequential activation and/or repression of different genetic programs. Therefore, CM differentiation and specification have been depicted as a step-wise specific chemical and mechanical stimuli inducing complete myogenic commitment and cell-cycle exit. Yet, the demonstration that some microRNAs are sufficient to direct ESC differentiation into CMs and that four specific miRNAs reprogram fibroblasts into CMs show that CM differentiation must also involve negative regulatory instructions. Here, we review the mechanisms of CM differentiation during development and from regenerative stem cells with a focus on the involvement of microRNAs in the process, putting in perspective their negative gene regulation as a main modifier of effective CM regeneration in the adult heart.Keywords
This publication has 237 references indexed in Scilit:
- MicroRNA Regulatory Networks in Cardiovascular DevelopmentDevelopmental Cell, 2010
- Wnt/β-Catenin Signaling: Components, Mechanisms, and DiseasesDevelopmental Cell, 2009
- Induced Pluripotent Stem Cells and Embryonic Stem Cells Are Distinguished by Gene Expression SignaturesCell Stem Cell, 2009
- MicroRNAs: Target Recognition and Regulatory FunctionsCell, 2009
- Mesp1 Coordinately Regulates Cardiovascular Fate Restriction and Epithelial-Mesenchymal Transition in Differentiating ESCsCell Stem Cell, 2008
- Targeted Deletion Reveals Essential and Overlapping Functions of the miR-17∼92 Family of miRNA ClustersCell, 2008
- MicroRNA Regulation of Cell Lineages in Mouse and Human Embryonic Stem CellsCell Stem Cell, 2008
- Origins and Fates of Cardiovascular Progenitor CellsCell, 2008
- Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined FactorsCell, 2007
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006