MicroRNA Cluster 302-367 Enhances Somatic Cell Reprogramming by Accelerating a Mesenchymal-to-Epithelial Transition

被引：213

作者：

Liao, Baojian ^{[1
,3
,4
]}

Bao, Xichen ^{[1
,2
,3
,4
]}

Liu, Longqi ^{[1
]}

Feng, Shipeng ^{[2
]}

Zovoilis, Athanasios ^{[5
]}

Liu, Wenbo ^{[1
]}

Xue, Yanting ^{[1
,3
,4
]}

Cai, Jie ^{[1
]}

Guo, Xiangpeng ^{[1
]}

Qin, Baoming ^{[1
]}

Zhang, Ruosi ^{[6
]}

Wu, Jiayan ^{[6
]}

Lai, Liangxue ^{[1
]}

Teng, Maikun ^{[3
,4
]}

Niu, Liwen ^{[3
,4
]}

Zhang, Biliang ^{[2
]}

Esteban, Miguel A. ^{[1
]}

Pei, Duanqing ^{[1
]}

机构：

[1] Chinese Acad Sci, Key Lab Regenerat Biol, S China Inst Stem Cell Biol & Regenerat Med, Guangzhou 510530, Guangdong, Peoples R China

[2] Chinese Acad Sci, Lab RNA Chem Biol, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China

[3] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China

[4] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China

[5] European Neurosci Inst Gottingen, D-37077 Gottingen, Germany

[6] Chinese Acad Sci, Key Lab Genome Sci & Informat, Beijing Inst Genom, Beijing 10029, Peoples R China

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2011年 / 286卷 / 19期

关键词：

EMBRYONIC STEM-CELLS; PLURIPOTENCY; DIFFERENTIATION; OCT4; ZEB1; SOX2; RNA;

D O I：

10.1074/jbc.C111.235960

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

MicroRNAs (miRNAs) are emerging critical regulators of cell function that frequently reside in clusters throughout the genome. They influence a myriad of cell functions, including the generation of induced pluripotent stem cells, also termed reprogramming. Here, we have successfully delivered entire miRNA clusters into reprogramming fibroblasts using retroviral vectors. This strategy avoids caveats associated with transient transfection of chemically synthesized miRNA mimics. Overexpression of 2 miRNA clusters, 106a-363 and in particular 302-367, allowed potent increases in induced pluripotent stem cell generation efficiency in mouse fibroblasts using 3 exogenous factors (Sox2, Klf4, and Oct4). Pathway analysis highlighted potential relevant effectors, including mesenchymal-to-epithelial transition, cell cycle, and epigenetic regulators. Further study showed that miRNA cluster 302-367 targeted TGF beta receptor 2, promoted increased E-cadherin expression, and accelerated mesenchymal-to-epithelial changes necessary for colony formation. Our work thus provides an interesting alternative for improving reprogramming using miRNAs and adds new evidence for the emerging relationship between pluripotency and the epithelial phenotype.

引用

页码：17359 / 17364

页数：6

共 20 条

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