Abstract 15093: MicroRna Profiling of Mouse Adult Cardiac Stem Cells Reveals Key Gene Expression Pathways for Differentiation and Proliferation Control
The recent identification of adult Cardiac Progenitor Cells (aCPC) changed the paradigm of the heart as a post mitotic organ. These cells can proliferate and differentiate into cardiomyocytes, endothelial and vascular smooth muscle cells, providing the potential for heart cell homoeostasis and therapeutic regeneration. aCPC may originate from remnants of Embryonic Heart Cells (EHC) or from circulating bone marrow Mesenchymal Stem Cells (MSC). microRNAs (miRs) are master switches controlling proliferation and differentiation and regulating stem cell and cardiac development and function. Modulation of miR regulated gene expression networks to control cell number and fate holds an exciting potential for novel therapeutic applications. To obtain an insight into the origin and function of aCPC we compared the expression profile of ∼100 miRs involved in stem cell and tissue differentiation control, with MSC and EHC. Mouse aCPC and MSC were isolated by flow cytometry according to the presence of membrane stem cell markers (sca-1, c-kit) and absence of haematopoyetic lineage markers; EHC were obtained from mouse embryonic hearts (day 9) and a comparative miR expression profile of three independent biological replicates was generated using a Real Time PCR based approach. Comparison of these cell populations based on unsupervised clustering of miR expression profiles shows that aCPC are a diverse population form MSC and EHC. aCPC cell samples clustered in an independent branch that could be distinguished on the basis of low expression of the 17-92 family miRs, known regulators of cell proliferation. However, aCPC were similar to EHC in the expression of key miR regulators of cardiac differentiation, which are absent from MSC cells. Additionally, aCPC differentially over-expressed a subset of miRs reported to be anti-proliferative. The most highly expressed miRs aCPCs are consistent with a quiescent and cardiac committed gene expression program. Interestingly, several of these miRs have also been reported to be upregulated in the cardiac hypertrophic response. These results provide novel insights into the gene expression regulation networks that control biologic properties of aCPCs, with possible implications in biotech and therapeutic applications.
- © 2011 by American Heart Association, Inc.