摘要
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,andα-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.
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-301 a in regulating cardiomyocyte differentiation of mouse embryonic stem(mES) cells, and provide experimental evidence for applying miR-301 a to the cardiomyocyte differentiation induction from stem cells.METHODS m ES cells with or without overexpression of miR-301 a 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, MEF2 C, andα-actinin were used to determine cardiomyocyte differentiation from mES cells.RESULTS High expression of miR-301 a was detected in the heart from late embryonic to neonatal mice. Overexpression of miR-301 a 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-301 a in cardiomyocytes. PTEN-regulated PI3 K-AKT-mTOR-Stat3 signaling showed involvement in regulating miR-301 a-promoted cardiomyocyte differentiation from mES cells.CONCLUSION MiR-301 a is capable of promoting embryonic stem cell differentiation to cardiomyocytes.
基金
Supported by the National Natural Science Foundation of China,No.81800243
the Science and Technology Commission of Shanghai Municipality,No.18411965900
the Fundamental Research Funds for the Central Universities,No.22120180125
