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We previously generated induced pluripotent stem cells (iPSCs) from dermal fibroblasts derived from the DFU patients, location\u2010matched skin of diabetic patients and normal healthy donors and re\u2010differentiated them into fibroblasts. To assess the epigenetic microRNA (miR) regulated changes triggered by cellular reprogramming, we performed miRs expression profiling. We found let\u20107c, miR\u201026b\u20105p, \u221229c\u20103p, \u2212148a\u20103p, \u2212196a\u20105p, \u2212199b\u20105p and \u2212374a\u20105p suppressed in iPSC\u2010derived fibroblasts in vitro and in 3D dermis\u2010like self\u2010assembly tissue, whereas their corresponding targets involved in cellular migration were upregulated. Moreover, targets involved in organization of extracellular matrix were induced after fibroblast reprogramming. PLAT gene, the crucial fibrinolysis factor, was upregulated in iPSC\u2010derived fibroblasts and was confirmed as a direct target of miR\u2010196a\u20105p. miR\u2010197\u20103p and miR\u2010331\u20103p were found upregulated specifically in iPSC\u2010derived diabetic fibroblasts, while their targets CAV1 and CDKN3 were suppressed. CAV1, an important negative regulator of wound healing, was confirmed as a direct miR\u2010197\u20103p target. Together, our findings demonstrate that iPSC reprogramming is an effective approach for erasing the diabetic non\u2010healing miR\u2010mediated epigenetic signature and promoting a pro\u2010healing cellular phenotype.<\/jats:p>","DOI":"10.1111\/exd.14405","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T11:48:18Z","timestamp":1623412098000},"page":"1065-1072","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cellular reprogramming of diabetic foot ulcer fibroblasts triggers pro\u2010healing miRNA\u2010mediated epigenetic signature"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0197-6198","authenticated-orcid":false,"given":"Irena","family":"Pastar","sequence":"first","affiliation":[{"name":"Wound Healing and Regenerative Medicine Research Program Dr Phillip Frost Department of Dermatology and Cutaneous Surgery University of Miami Miller 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Cutaneous Surgery University of Miami Miller School of Medicine Miami FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Kashpur","sequence":"additional","affiliation":[{"name":"Department of Cell, Molecular, and Developmental Biology Sackler School of Graduate Biomedical Sciences Tufts University Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5114-9524","authenticated-orcid":false,"given":"Ivan","family":"Jozic","sequence":"additional","affiliation":[{"name":"Wound Healing and Regenerative Medicine Research Program Dr Phillip Frost Department of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine Miami FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheyanne R.","family":"Head","sequence":"additional","affiliation":[{"name":"Wound Healing and Regenerative Medicine Research Program Dr Phillip Frost Department of Dermatology and 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