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miR-203 imposes an intrinsic barrier during cellular reprogramming by targeting NFATC2

View ORCID ProfileMaría Salazar-Roa, Sara Martínez-Martínez, Osvaldo Graña-Castro, Mónica Álvarez-Fernández, Marianna Trakala, Juan-Miguel Redondo, View ORCID ProfileMarcos Malumbres
doi: https://doi.org/10.1101/2020.06.02.131136
María Salazar-Roa
1Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
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  • ORCID record for María Salazar-Roa
Sara Martínez-Martínez
2Genetic Regulation, Vascular Remodeling and Inflammation group, Spanish National Cardiovascular Research Center (CNIC), Madrid, Spain
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Osvaldo Graña-Castro
3Bioinformatics Unit, CNIO, Madrid, Spain
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Mónica Álvarez-Fernández
1Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
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Marianna Trakala
1Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
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Juan-Miguel Redondo
2Genetic Regulation, Vascular Remodeling and Inflammation group, Spanish National Cardiovascular Research Center (CNIC), Madrid, Spain
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Marcos Malumbres
1Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
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  • ORCID record for Marcos Malumbres
  • For correspondence: malumbres@cnio.es
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Abstract

Cellular reprogramming from somatic to pluripotent cells is the basis for multiple applications aimed to replace damaged tissues in regenerative medicine. However, this process is limited by intrinsic barriers that are induced in response to reprogramming factors. In this manuscript we report that miR-203, a microRNA with multiple functions in differentiation and tumor suppression, acts as an endogenous barrier to reprogramming. Genetic ablation of miR-203 results in enhanced reprogramming whereas its expression prevents the formation of pluripotent cells both in vitro and in vivo. Mechanistically, this effect correlates with the direct repression of NFATC2, a transcription factor involved in the early phases of reprogramming. Inhibition of NFATC2 mimics miR-203 effects whereas NFATC2 overexpression rescues inducible cell pluripotency in miR-203-overexpressing cultures. These data suggest that miR-203 repression may favor the efficiency of reprogramming in a variety of cellular models.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted June 04, 2020.
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miR-203 imposes an intrinsic barrier during cellular reprogramming by targeting NFATC2
María Salazar-Roa, Sara Martínez-Martínez, Osvaldo Graña-Castro, Mónica Álvarez-Fernández, Marianna Trakala, Juan-Miguel Redondo, Marcos Malumbres
bioRxiv 2020.06.02.131136; doi: https://doi.org/10.1101/2020.06.02.131136
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miR-203 imposes an intrinsic barrier during cellular reprogramming by targeting NFATC2
María Salazar-Roa, Sara Martínez-Martínez, Osvaldo Graña-Castro, Mónica Álvarez-Fernández, Marianna Trakala, Juan-Miguel Redondo, Marcos Malumbres
bioRxiv 2020.06.02.131136; doi: https://doi.org/10.1101/2020.06.02.131136

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