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p73 regulates epidermal wound healing and induced keratinocyte programming

dc.contributor.authorBeeler, J. Scott
dc.contributor.authorMarshall, Clayton B.
dc.contributor.authorGonzalez-Ericsson, Paula I.
dc.contributor.authorShaver, Timothy M.
dc.contributor.authorGuasch, Gabriela L. Santos
dc.contributor.authorLea, Spencer T.
dc.contributor.authorJohnson, Kimberly N.
dc.contributor.authorJin, Hailing
dc.contributor.authorVenters, Bryan J.
dc.contributor.authorSanders, Melinda E.
dc.contributor.authorPietenpol, Jennifer A.
dc.identifier.citationBeeler JS, Marshall CB, Gonzalez-Ericsson PI, Shaver TM, Santos Guasch GL, Lea ST, et al. (2019) p73 regulates epidermal wound healing and induced keratinocyte programming. PLoS ONE 14(6): e0218458.
dc.description.abstractp63 is a transcriptional regulator of ectodermal development that is required for basal cell proliferation and stem cell maintenance. p73 is a closely related p53 family member that is expressed in select p63-positive basal cells and can heterodimerize with p63. p73-/- mice lack multiciliated cells and have reduced numbers of basal epithelial cells in select tissues; however, the role of p73 in basal epithelial cells is unknown. Herein, we show that p73-deficient mice exhibit delayed wound healing despite morphologically normal-appearing skin. The delay in wound healing is accompanied by decreased proliferation and increased levels of biomarkers of the DNA damage response in basal keratinocytes at the epidermal wound edge. In wild-type mice, this same cell population exhibited increased p73 expression after wounding. Analyzing single-cell transcriptomic data, we found that p73 was expressed by epidermal and hair follicle stem cells, cell types required for wound healing. Moreover, we discovered that p73 isoforms expressed in the skin (Delta Np73) enhance p63-mediated expression of keratinocyte genes during cellular reprogramming from a mesenchymal to basal keratinocyte-like cell. We identified a set of 44 genes directly or indirectly regulated by Delta Np73 that are involved in skin development, cell junctions, cornification, proliferation, and wound healing. Our results establish a role for p73 in cutaneous wound healing through regulation of basal keratinocyte function.en_US
dc.description.sponsorshipThis research was supported by National Institutes of Health (NIH) grants R01CA105436, R01CA070856, P50CA098131, and P30CA068485 to JAP and NIH Vanderbilt Medical Scientist Training Program (T32GM007347) grant support to JSB. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.publisherPlos Oneen_US
dc.rightsCopyright: © 2019 Beeler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.subjectHAIR FOLLICLEen_US
dc.subjectHISTONE H2AXen_US
dc.subjectP53 HOMOLOGen_US
dc.titlep73 regulates epidermal wound healing and induced keratinocyte programmingen_US

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