biostudies-literaturePal DU.S. Department of Health & Human Services | NIH | National Institute of General Medical SciencesNIDDK NIH HHSNINDS NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Nursing ResearchNIGMS NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases1129https://www.ebi.ac.uk/biostudies/studies/S-EPMC9975176biostudies-literatureUnknown14(1)Tissue injury to skin diminishes miR-200b in dermal fibroblasts. Fibroblasts are widely reported to directly reprogram into endothelial-like cells and we hypothesized that miR-200b inhibition may cause such changes. We transfected human dermal fibroblasts with anti-miR-200b oligonucleotide, then using single cell RNA sequencing, identified emergence of a vasculogenic subset with a distinct fibroblast transcriptome and demonstrated blood vessel forming function in vivo. Anti-miR-200b delivery to murine injury sites likewise enhanced tissue perfusion, wound closure, and vasculogenic fibroblast contribution to perfused vessels in a FLI1 dependent manner. Vasculogenic fibroblast subset emergence was blunted in delayed healing wounds of diabetic animals but, topical tissue nanotransfection of a single anti-miR-200b oligonucleotide was sufficient to restore FLI1 expression, vasculogenic fibroblast emergence, tissue perfusion, and wound healing. Augmenting a physiologic tissue injury adaptive response mechanism that produces a vasculogenic fibroblast state change opens new avenues for therapeutic tissue vascularization of ischemic wounds.Nature communicationsIdentification of a physiologic vasculogenic fibroblast state to achieve tissue repair.PMC9975176R01 GM077185DK128845R01 NS042617R01 DK128845GM077185R01 GM108014R01 DK076566NS042617R01 NS085272GM108014Ghatak SRustagi YBhasme PTabasum SKumar MPal DKacar SLiu SGnyawali SCAbouhashem ASHernandez ELiu YSharma ASingh KKhanna SRoy SEl Masry MSWan JGorain MKhona DKVerma SSSen CKMohanty SKVerma PCastro NHSrivastava RLawrence WMoore JPalakurti RPerez DGReese DGhosh NYoder MCfalseIdentification of a physiologic vasculogenic fibroblast state to achieve tissue repair.Tissue injury to skin diminishes miR-200b in dermal fibroblasts. Fibroblasts are widely reported to directly reprogram into endothelial-like cells and we hypothesized that miR-200b inhibition may cause such changes. We transfected human dermal fibroblasts with anti-miR-200b oligonucleotide, then using single cell RNA sequencing, identified emergence of a vasculogenic subset with a distinct fibroblast transcriptome and demonstrated blood vessel forming function in vivo. Anti-miR-200b delivery to murine injury sites likewise enhanced tissue perfusion, wound closure, and vasculogenic fibroblast contribution to perfused vessels in a FLI1 dependent manner. Vasculogenic fibroblast subset emergence was blunted in delayed healing wounds of diabetic animals but, topical tissue nanotransfection of a single anti-miR-200b oligonucleotide was sufficient to restore FLI1 expression, vasculogenic fibroblast emergence, tissue perfusion, and wound healing. Augmenting a physiologic tissue injury adaptive response mechanism that produces a vasculogenic fibroblast state change opens new avenues for therapeutic tissue vascularization of ischemic wounds.2023-01-01T00:00:00Z2023 Feb2024-11-21T08:17:07.266Z2024-11-21T08:17:07.266ZS-EPMC99751763685474910.1038/s41467-023-36665-z