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microRNA-184 induces a commitment switch to epidermal differentiation

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Item Type:Article
Title:microRNA-184 induces a commitment switch to epidermal differentiation
Creators Name:Nagosa, S. and Leesch, F. and Putin, D. and Bhattacharya, S. and Altshuler, A. and Serror, L. and Amitai-Lange, A. and Nasser, W. and Aberdam, E. and Rouleau, M. and Tattikota, S.G. and Poy, M.N. and Aberdam, D. and Shalom-Feuerstein, R.
Abstract:miR-184 is a highly evolutionary conserved microRNA (miRNA) from fly to human. The importance of miR-184 was underscored by the discovery that point mutations in miR-184 gene led to corneal/lens blinding disease. However, miR-184-related function in vivo remained unclear. Here, we report that the miR-184 knockout mouse model displayed increased p63 expression in line with epidermal hyperplasia, while forced expression of miR-184 by stem/progenitor cells enhanced the Notch pathway and induced epidermal hypoplasia. In line, miR-184 reduced clonogenicity and accelerated differentiation of human epidermal cells. We showed that by directly repressing cytokeratin 15 (K15) and FIH1, miR-184 induces Notch activation and epidermal differentiation. The disease-causing miR-184C57U mutant failed to repress K15 and FIH1 and to induce Notch activation, suggesting a loss-of-function mechanism. Altogether, we propose that, by targeting K15 and FIH1, miR-184 regulates the transition from proliferation to early differentiation, while mis-expression or mutation in miR-184 results in impaired homeostasis.
Keywords:microRNA, miR-184, miRNA-184, K15, FIH1, Notch, Stem Cells, Epidermis, Hair Follicle, Cornea, Animals, Mice
Source:Stem Cell Reports
ISSN:2213-6711
Publisher:Cell Press / Elsevier
Volume:9
Number:6
Page Range:1991-2004
Date:12 December 2017
Official Publication:https://doi.org/10.1016/j.stemcr.2017.10.030
PubMed:View item in PubMed

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