Journal
STEM CELLS
Volume 31, Issue 10, Pages 2266-2272Publisher
WILEY
DOI: 10.1002/stem.1465
Keywords
Differentiation; Embryonic Stem Cells; miRNA; Ectoderm; Mesndoderm; Pax6; miR-290-295
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Funding
- Israel Science Foundation [730/12, 1541/ 09]
- Helen and Martin Kimmel Institute for Stem Cell Research
- Leona M. and Harry B. Helmsley Charitable Trust
- Carolito Stiftung, Y. Leon Benoziyo Institute for Molecular Medicine, Charlene Vener New Scientist Fund, Estates of Fannie Sherr, Lola Asseof, Nathan Baltor, Maria Halphen, Julius and Ray Charlestein Foundation
- Fraida Foundation
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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. Stem Cells 2013;31:2266-2272
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