MiR-301a promotes embryonic stem cell differentiation to cardiomyocytes
Open Access
- 26 December 2019
- journal article
- research article
- Published by Baishideng Publishing Group Inc. in World Journal of Stem Cells
- Vol. 11 (12), 1130-1141
- https://doi.org/10.4252/wjsc.v11.i12.1130
Abstract
BACKGROUND Cardiovascular disease is the leading cause of death worldwide. Tissue repair after pathological injury in the heart remains a major challenge due to the limited regenerative ability of cardiomyocytes in adults. Stem cell-derived cardiomyocytes provide a promising source for the cell transplantation-based treatment of injured hearts. AIM To explore the function and mechanisms of miR-301a in regulating cardiomyocyte differentiation of mouse embryonic stem (mES) cells, and provide experimental evidence for applying miR-301a to the cardiomyocyte differentiation induction from stem cells. METHODS mES cells with or without overexpression of miR-301a were applied for all functional assays. The hanging drop technique was applied to form embryoid bodies from mES cells. Cardiac markers including GATA-4, TBX5, MEF2C, and alpha-actinin were used to determine cardiomyocyte differentiation from mES cells. RESULTS High expression of miR-301a was detected in the heart from late embryonic to neonatal mice. Overexpression of miR-301a in mES cells significantly induced the expression of cardiac transcription factors, thereby promoting cardiomyocyte differentiation and beating cardiomyocyte clone formation. PTEN is a target gene of miR-301a in cardiomyocytes. PTEN-regulated PI3K-AKT-mTOR-Stat3 signaling showed involvement in regulating miR-301a-promoted cardiomyocyte differentiation from mES cells. CONCLUSION MiR-301a is capable of promoting embryonic stem cell differentiation to cardiomyocytes.Keywords
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