微小RNA-301a促进胚胎干细胞向心肌细胞分化。
MiR-301a promotes embryonic stem cell differentiation to cardiomyocytes.
作者信息
Zhen Li-Xiao, Gu Yu-Ying, Zhao Qian, Zhu Hui-Fang, Lv Jin-Hui, Li Shu-Jun, Xu Zhen, Li Li, Yu Zuo-Ren
机构信息
Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200120, China.
Department of Microbiology and Immunology, Wenzhou Medical College, Wenzhou 325000, Zhejiang Province, China.
出版信息
World J Stem Cells. 2019 Dec 26;11(12):1130-1141. doi: 10.4252/wjsc.v11.i12.1130.
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. 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.
背景
心血管疾病是全球主要的死亡原因。由于成人心肌细胞的再生能力有限，心脏病理损伤后的组织修复仍然是一项重大挑战。干细胞衍生的心肌细胞为基于细胞移植的受损心脏治疗提供了一个有前景的来源。
目的
探讨miR-301a在调节小鼠胚胎干细胞（mES）向心肌细胞分化中的作用及机制，为将miR-301a应用于干细胞诱导分化为心肌细胞提供实验依据。
方法
对过表达或未过表达miR-301a的mES细胞进行所有功能检测。采用悬滴法由mES细胞形成胚状体。使用包括GATA-4、TBX5、MEF2C和α-肌动蛋白在内的心脏标志物来确定mES细胞向心肌细胞的分化。
结果
在胚胎晚期至新生小鼠的心脏中检测到miR-301a的高表达。mES细胞中miR-301a的过表达显著诱导心脏转录因子的表达，从而促进心肌细胞分化和搏动性心肌细胞克隆形成。PTEN是miR-301a在心肌细胞中的靶基因。PTEN调节的PI3K-AKT-mTOR-Stat3信号通路参与调节miR-301a促进mES细胞向心肌细胞的分化。
结论
MiR-301a能够促进胚胎干细胞向心肌细胞分化。
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