title: MicroRNA cluster 302-367 enhances somatic cell reprogramming by accelerating a mesenchymal-to-epithelial transition.
abstract: 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 TGFβ 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.
authors: Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Chinese Academy of Sciences, Guangzhou 510530, China.
authors: Baojian
authors: B
authors: Liao
authors: Xichen
authors: X
authors: Bao
authors: Longqi
authors: L
authors: Liu
authors: Shipeng
authors: S
authors: Feng
authors: Athanasios
authors: A
authors: Zovoilis
authors: Wenbo
authors: W
authors: Liu
authors: Yanting
authors: Y
authors: Xue
authors: Jie
authors: J
authors: Cai
authors: Xiangpeng
authors: X
authors: Guo
authors: Baoming
authors: B
authors: Qin
authors: Ruosi
authors: R
authors: Zhang
authors: Jiayan
authors: J
authors: Wu
authors: Liangxue
authors: L
authors: Lai
authors: Maikun
authors: M
authors: Teng
authors: Liwen
authors: L
authors: Niu
authors: Biliang
authors: B
authors: Zhang
authors: Miguel A
authors: MA
authors: Esteban
authors: Duanqing
authors: D
authors: Pei
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D000090062:Kruppel-Like Factor 4; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; C542541:MIRN106 microRNA, human; C558265:MIRN302 microRNA, mouse; C532169:MIRN302A microRNA, human; D035683:MicroRNAs; C543896:Mirn106 microRNA, mouse; D016212:Transforming Growth Factor beta