Published online Dec 26, 2019. doi: 10.4252/wjsc.v11.i12.1130
Peer-review started: June 19, 2019
First decision: July 31, 2019
Revised: September 23, 2019
Accepted: October 14, 2019
Article in press: October 14, 2019
Published online: December 26, 2019
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.
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.
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 α-actinin were used to determine cardiomyocyte differentiation from mES cells.
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.
MiR-301a is capable of promoting embryonic stem cell differentiation to cardiomyocytes.
Core tip: MiR-301a was identified as a miRNA highly enriched in the heart from late embryonic to neonatal mice. Overexpression of miR-301a significantly induced the expression of cardiac transcription factors and promoted cardiomyocyte differentiation of mouse embryonic stem cells. These findings will help improve the efficiency of cardiomyocyte differentiation from stem cells, and strengthen the potential of cell therapeutics to treat heart failure caused by myocardial infarction.