microRNA-184 Induces a Commitment Switch to Epidermal Differentiation
Summary: 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 th...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-12-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221367111730485X |
| _version_ | 1818005558021586944 |
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| author | Sara Nagosa Friederike Leesch Daria Putin Swarnabh Bhattacharya Anna Altshuler Laura Serror Aya Amitai-Lange Waseem Nasser Edith Aberdam Matthieu Rouleau Sudhir G. Tattikota Matthew N. Poy Daniel Aberdam Ruby Shalom-Feuerstein |
| author_facet | Sara Nagosa Friederike Leesch Daria Putin Swarnabh Bhattacharya Anna Altshuler Laura Serror Aya Amitai-Lange Waseem Nasser Edith Aberdam Matthieu Rouleau Sudhir G. Tattikota Matthew N. Poy Daniel Aberdam Ruby Shalom-Feuerstein |
| author_sort | Sara Nagosa |
| collection | DOAJ |
| description | Summary: 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. : Using new genetic mouse models and study of human epidermal cells, Nagosa et al. show that miR-184 regulates epidermal proliferation and commitment to differentiation. The authors discovered that miR-184 directly represses K15 and FIH1, which are important for the maintenance of stemness phenotype. Keywords: microRNA, miR-184, miRNA-184, K15, FIH1, notch, stem cells, epidermis, hair follicle, cornea |
| first_indexed | 2024-04-14T04:45:37Z |
| format | Article |
| id | doaj.art-820af42a71f64d11a72a250c49004c75 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-04-14T04:45:37Z |
| publishDate | 2017-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-820af42a71f64d11a72a250c49004c752022-12-22T02:11:28ZengElsevierStem Cell Reports2213-67112017-12-019619912004microRNA-184 Induces a Commitment Switch to Epidermal DifferentiationSara Nagosa0Friederike Leesch1Daria Putin2Swarnabh Bhattacharya3Anna Altshuler4Laura Serror5Aya Amitai-Lange6Waseem Nasser7Edith Aberdam8Matthieu Rouleau9Sudhir G. Tattikota10Matthew N. Poy11Daniel Aberdam12Ruby Shalom-Feuerstein13Department of Genetics and Developmental Biology, The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, IsraelDepartment of Genetics and Developmental Biology, The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, IsraelDepartment of Genetics and Developmental Biology, The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, IsraelDepartment of Genetics and Developmental Biology, The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, IsraelDepartment of Genetics and Developmental Biology, The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, IsraelDepartment of Genetics and Developmental Biology, The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, IsraelDepartment of Genetics and Developmental Biology, The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, IsraelDepartment of Genetics and Developmental Biology, The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, IsraelUniversity Paris Diderot, Sorbonne Paris Cité, Paris 75475, France; INSERM U976, Hôpital St-Louis, Paris 75010, FranceCNRS, LP2M, UMR7370, Faculté de Médecine, Nice, France; Université Nice Sophia Antipolis, Nice, FranceMax Delbrueck Center for Molecular Medicine, Robert Roessle Strasse 10, Berlin 13125, GermanyMax Delbrueck Center for Molecular Medicine, Robert Roessle Strasse 10, Berlin 13125, GermanyUniversity Paris Diderot, Sorbonne Paris Cité, Paris 75475, France; INSERM U976, Hôpital St-Louis, Paris 75010, FranceDepartment of Genetics and Developmental Biology, The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, Israel; Corresponding authorSummary: 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. : Using new genetic mouse models and study of human epidermal cells, Nagosa et al. show that miR-184 regulates epidermal proliferation and commitment to differentiation. The authors discovered that miR-184 directly represses K15 and FIH1, which are important for the maintenance of stemness phenotype. Keywords: microRNA, miR-184, miRNA-184, K15, FIH1, notch, stem cells, epidermis, hair follicle, corneahttp://www.sciencedirect.com/science/article/pii/S221367111730485X |
| spellingShingle | Sara Nagosa Friederike Leesch Daria Putin Swarnabh Bhattacharya Anna Altshuler Laura Serror Aya Amitai-Lange Waseem Nasser Edith Aberdam Matthieu Rouleau Sudhir G. Tattikota Matthew N. Poy Daniel Aberdam Ruby Shalom-Feuerstein microRNA-184 Induces a Commitment Switch to Epidermal Differentiation Stem Cell Reports |
| title | microRNA-184 Induces a Commitment Switch to Epidermal Differentiation |
| title_full | microRNA-184 Induces a Commitment Switch to Epidermal Differentiation |
| title_fullStr | microRNA-184 Induces a Commitment Switch to Epidermal Differentiation |
| title_full_unstemmed | microRNA-184 Induces a Commitment Switch to Epidermal Differentiation |
| title_short | microRNA-184 Induces a Commitment Switch to Epidermal Differentiation |
| title_sort | microrna 184 induces a commitment switch to epidermal differentiation |
| url | http://www.sciencedirect.com/science/article/pii/S221367111730485X |
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