Abstract
Myc is an essential regulator of cell growth and proliferation. Myc overexpression promotes the homeostatic expansion of cardiomyocyte populations by cell competition, however whether this applies to other cardiac lineages remains unknown. The epicardium contributes signals and cells to the developing and adult injured heart and exploring strategies for modulating its activity is of great interest. Using inducible genetic mosaics, we overexpressed Myc in the epicardium and determined the differential expansion of Myc-overexpressing cells with respect to their wild type counterparts. Myc-overexpressing cells overcolonized all epicardial-derived lineages and showed increased ability to invade the myocardium and populate the vasculature. We also found massive colonization of the myocardium by Wt1Cre-derived Myc-overexpressing cells, with preservation of cardiac development. Detailed analyses showed that this contribution is unlikely to derive from Cre activity in early cardiomyocytes but does not either derive from established epicardial cells, suggesting that early precursors expressing Wt1Cre originate the recombined cardiomyocytes. Myc overexpression does not modify the initial distribution of Wt1Cre-recombined cardiomyocytes, indicating that it does not stimulate the incorporation of early expressing Wt1Cre lineages to the myocardium, but differentially expands this initial population. We propose that strategies using epicardial lineages for heart repair may benefit from promoting cell competitive ability.
Highlights
Factor which has been involved in many normal and pathological processes[21,22]
We studied whether cell competition modifies the myocardial colonization pattern of Epicardial-derived cells (EPDCs), determining the preferential expansion of Myc-enhanced epicardial cells in the niches usually colonized by EPDCs and in the cardiomyocyte lineage
The tissues colonized by EPDCs have multiple origins, with EPDCs contributing to only a fraction of these tissues
Summary
The postnatal epicardium is normally quiescent, it shows cellular and signaling activation upon injury in the fish and the mouse, contributing cells and signals that could be relevant in cardiac repair processes[9,23,24,25]. Increasing anabolism by moderate Myc overexpression in a mosaic fashion leads to cardiomyocyte competition during cardiac development and adult myocardium homeostasis[29]. Cell competition leads to the homeostatic replacement of wild type cardiomyocytes by the Myc-enhanced cardiomyocytes without producing any cardiac anatomical or functional alteration[29]. We studied whether cell competition modifies the myocardial colonization pattern of EPDCs, determining the preferential expansion of Myc-enhanced epicardial cells in the niches usually colonized by EPDCs and in the cardiomyocyte lineage
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
