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| Item Type: | Article |
|---|---|
| Title: | microRNA-184 induces a commitment switch to epidermal differentiation |
| Creators Name: | Nagosa, S., Leesch, F., Putin, D., Bhattacharya, S., Altshuler, A., Serror, L., Amitai-Lange, A., Nasser, W., Aberdam, E., Rouleau, M., Tattikota, S.G., Poy, M.N., 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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