title: Pluripotency-associated miR-290/302 family of microRNAs promote the dismantling of naive pluripotency.
abstract: The molecular mechanism controlling the dismantling of naive pluripotency is poorly understood. Here we show that microRNAs (miRNAs) have important roles during naive to primed pluripotency transition. Dgcr8(-/-) embryonic stem cells (ESCs) failed to completely silence the naive pluripotency program, as well as to establish the primed pluripotency program during differentiation. miRNA profiling revealed that expression levels of a large number of miRNAs changed dynamically and rapidly during naive to primed pluripotency transition. Furthermore, a miRNA screen identified numerous miRNAs promoting naive to primed pluripotency transition. Unexpectedly, multiple miRNAs from miR-290 and miR-302 clusters, previously shown as pluripotency-promoting miRNAs, demonstrated the strongest effects in silencing naive pluripotency. Knockout of both miR-290 and miR-302 clusters but not either alone blocked the silencing of naive pluripotency program. Mechanistically, the miR-290/302 family of miRNAs may facilitate the exit of naive pluripotency in part by promoting the activity of MEK pathway and through directly repressing Akt1. Our study reveals miRNAs as an important class of regulators potentiating ESCs to transition from naive to primed pluripotency, and uncovers context-dependent functions of the miR-290/302 family of miRNAs at different developmental stages.
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Science, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Gu
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Science, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Science, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100083, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Science, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Duan
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Science, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hao
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Science, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Xi-Wen
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Science, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Science, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Da-Ren
authors.initials: DR
authors.lastname: Wu
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Science, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Guo
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking-Tsinghua Center for Life Science, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Yangming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000201:enzymology / Q000378:metabolism*; D020868:Gene Silencing; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000201:enzymology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics
chemical_list: C474044:Dgcr8 protein, mouse; C547384:MIRN290 microRNA, mouse; C558265:MIRN302 microRNA, mouse; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases