miR-302 regulates pluripotency, teratoma formation and differentiation in stem cells via an AKT1/OCT4-dependent manner

被引：35

作者：

Li, H-L ^{[1
]}

Wei, J-F ^{[1
,2
]}

Fan, L-Y ^{[1
]}

Wang, S-H ^{[1
]}

Zhu, L. ^{[3
]}

Li, T-P ^{[1
]}

Lin, G. ^{[4
]}

Sun, Y. ^{[5
]}

Sun, Z-J ^{[3
]}

Ding, J. ^{[3
]}

Liang, X-L ^{[1
]}

Li, J. ^{[1
]}

Han, Q. ^{[1
]}

Zhao, R-C-H ^{[1
,6
]}

机构：

[1] Chinese Acad Med Sci, Inst Basic Med Sci, Peking Union Med Coll, Dept Cell Biol,Sch Basic Med,Tissue Engn Ctr, Beijing 100730, Peoples R China

[2] Xuzhou Med Univ, Sch Basic Med Sci, Dept Histol & Embryol, Xuzhou, Peoples R China

[3] Beijing Union Med Coll Hosp, Dept Obstet & Gynecol, Beijing, Peoples R China

[4] Cent S Univ, Minist Hlth, Key Lab Stem Cells & Reprod Engn, Inst Reprod & Stem Cell Engn, Changsha, Hunan, Peoples R China

[5] Beijing Union Med Coll Hosp, Dept Nucl Med, Beijing, Peoples R China

[6] Beijing Union Med Coll Hosp, Beijing, Peoples R China

来源：

CELL DEATH & DISEASE | 2016年 / 7卷

基金：

中国国家自然科学基金;

关键词：

EMBRYONAL CARCINOMA-CELLS; SELF-RENEWAL; INITIATING CELLS; SIGNALING PATHWAYS; TUMOR PROGRESSION; HUMAN FIBROBLASTS; OVARIAN-CANCER; ES CELLS; MICRORNAS; CYCLE;

D O I：

10.1038/cddis.2015.383

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Pluripotency makes human pluripotent stem cells (hPSCs) promising for regenerative medicine, but the teratoma formation has been considered to be a major obstacle for their clinical applications. Here, we determined that the downregulation of miR-302 suppresses the teratoma formation, hampers the self-renewal and pluripotency, and promotes hPSC differentiation. The underlying mechanism is that the high endogenous expression of miR-302 suppresses the AKT1 expression by directly targeting its 3'UTR and subsequently maintains the pluripotent factor OCT4 at high level. Our findings reveal that miR-302 regulates OCT4 by suppressing AKT1, which provides hPSCs two characteristics related to their potential for clinical applications: the benefit of pluripotency and the hindrance of teratoma formation. More importantly, we demonstrate that miR-302 upregulation cannot lead OCT4 negative human adult mesenchymal stem cells (hMSCs) to acquire the teratoma formation in vivo. Whether miR-302 upregulation can drive hMSCs to acquire a higher differentiation potential is worthy of deep investigation.

引用

页码：e2078 / e2078

页数：14

共 66 条

[11] Identification of a tumor-initiating stem cell population in human renal carcinomas [J].