MiR-301a promotes embryonic stem cell differentiation to cardiomyocytes

doi:10.4252/wjsc.v11.i12.1130

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World Journal of Stem Cells

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Basic Study

World J Stem Cells. Dec 26, 2019; 11(12): 1130-1141
Published online Dec 26, 2019. doi: 10.4252/wjsc.v11.i12.1130

MiR-301a promotes embryonic stem cell differentiation to cardiomyocytes

Li-Xiao Zhen, Yu-Ying Gu, Qian Zhao, Hui-Fang Zhu, Jin-Hui Lv, Shu-Jun Li, Zhen Xu, Li Li, Zuo-Ren Yu

Li-Xiao Zhen, Yu-Ying Gu, Qian Zhao, Hui-Fang Zhu, Jin-Hui Lv, Shu-Jun Li, Li Li, Zuo-Ren Yu, Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China

Li-Xiao Zhen, Yu-Ying Gu, Qian Zhao, Jin-Hui Lv, Shu-Jun Li, Li Li, Zuo-Ren Yu, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China

Zhen Xu, Department of Microbiology and Immunology, Wenzhou Medical College, Wenzhou 325000, Zhejiang Province, China

Author contributions: Zhen LX, Zhao Q, Zhu HF, Lv JH, Li SJ, and Xu Z performed the experiments; Li L and Zhao Q performed the data analysis; Yu ZR and Gu YY designed the project and wrote the paper.

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.

Institutional animal care and use committee statement: Animal studies were approved by the Institutional Animal Care and Use Committee of the Tongji University School of Medicine (No. TJLAC-016-028).

Conflict-of-interest statement: There are no conflicts of interest associated with this manuscript.

Corresponding author: Zuo-Ren Yu, PhD, Professor, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China. zuoren.yu@tongji.edu.cn

Telephone: +86-21-61569842 Fax: +86-21-61569842

Received: June 17, 2019
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
Processing time: 168 Days and 21 Hours

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 α-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: miR-301a; Mouse embryonic stem cells; Differentiation; 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.