Abstract
The identification of cardiac cells with stem cell properties changed the paradigm of the heart as a post mitotic organ. These cells proliferate and differentiate into cardiomyocytes, endothelial and vascular smooth muscle cells, providing for cardiac cell homeostasis and regeneration. microRNAs are master switches controlling proliferation and differentiation, in particular regulating stem cell biology and cardiac development. Modulation of microRNAs -regulated gene expression networks holds the potential to control cell fate and proliferation, with predictable biotechnologic and therapeutic applications. To obtain insights into the regulatory networks active in cardiac stem cells, we characterized the expression profile of 95 microRNAs with reported functions in stem cell and tissue differentiation in mouse cardiac stem cells, and compared it to that of mouse embryonic heart and mesenchymal stem cells. The most highly expressed microRNAs identified in cardiac stem cells are known to target key genes involved in the control of cell proliferation and adhesion, vascular function and cardiomyocyte differentiation. We report a subset of differentially expressed microRNAs that are proposed to act as regulators of differentiation and proliferation of adult cardiac stem cells, providing novel insights into active gene expression networks regulating their biological properties.
Highlights
The observation of cardiomyocyte division first questioned the paradigm that the mammalian heart is a post-mitotic organ
To obtain high quality total RNA samples in order to characterize the adult cardiac stem cells (CSCs) miR expression profile, we developed a method to isolated cells from mice hearts by soft mechanical destruction of cardiac tissue, followed by Sca-1 antigen labeling and Fluorescence Activated Cell Sorting (FACS) sorting (Figure S1)
Our results provide new insights into active regulatory networks underlying the control of proliferation and differentiation, two critical aspects of CSC biology
Summary
The observation of cardiomyocyte division first questioned the paradigm that the mammalian heart is a post-mitotic organ. CSCs are undifferentiated, keep quiescent until induced to proliferate and may differentiate into one of the three cardiac cell lineages: cardiomyocytes, endothelial cells and vascular smooth muscle cells. The origin of the CSC population remains unclear. They are either believed to be the progeny of mesenchymal cells from the bone marrow, which homed to the heart through systemic circulation, or to correspond to cellular remnants of the embryonic heart [3]. A tightly orchestrated gene expression program involving cardiac specific genes and transcription factors that are activated in succession is initiated, coordinating heart development, along with the differentiation of the main cardiac cell lineages [4]. Genes that control cardiac formation during development are active in CSCs
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