title: Brief report: miR-290-295 regulate embryonic stem cell differentiation propensities by repressing Pax6.
abstract: microRNAs of the miR-290-295 family are selectively expressed at high levels in mouse embryonic stem cells (mESCs) and have established roles in regulating self-renewal. However, the potential influence of these microRNAs on cell fate acquisition during differentiation has been overlooked. Here, we show that miR-290-295 regulate the propensity of mESCs to acquire specific fates. We generated a new miR-290-295-null mESC model, which exhibits increased propensity to generate ectoderm, at the expense of endoderm and mesoderm lineages. We further found that in wild-type cells, miR-290-295 repress Pax6 and ectoderm differentiation; accordingly, Pax6 knockdown partially rescues the mESCs differentiation impairment that is caused by loss of miR-290-295. Thus, in addition to regulating self-renewal, the large reservoir of miR-290-295 in undifferentiated mESCs fine-tunes the expression of master transcriptional factors, such as Pax6, thereby regulating the equilibrium of fate acquisition by mESC descendants.
authors.affiliation: Department of Biological Chemistry and Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Haggai
authors.initials: H
authors.lastname: Kaspi
authors.forename: Elik
authors.initials: E
authors.lastname: Chapnik
authors.forename: Maayan
authors.initials: M
authors.lastname: Levy
authors.forename: Gilad
authors.initials: G
authors.lastname: Beck
authors.forename: Eran
authors.initials: E
authors.lastname: Hornstein
authors.forename: Yoav
authors.initials: Y
authors.lastname: Soen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004475:Ectoderm / Q000166:cytology; D053595:Embryonic Stem Cells / Q000502:physiology*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; C547384:MIRN290 microRNA, mouse; C561933:MIRN295 microRNA, mouse; D035683:MicroRNAs; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins
keywords: Differentiation; Ectoderm; Embryonic Stem Cells; Mesndoderm; Pax6; miR-290-295; miRNA