Pal, DurbaGhatak, SubhadipSingh, KanhaiyaAbouhashem, Ahmed SafwatKumar, ManishekharEl Masry, Mohamed S.Mohanty, Sujit K.Palakurti, RavichandRustagi, YashikaTabasum, SabaKhona, Dolly K.Khanna, SavitaKacar, SedatSrivastava, RajneeshBhasme, PramodVerma, Sumit S.Hernandez, EdwardSharma, AnuReese, DiamondVerma, PriyankaGhosh, NandiniGorain, MahadeoWan, JunLiu, ShengLiu, YunlongCastro, Natalia HiguitaGnyawali, Surya C.Lawrence, WilliamMoore, JordanPerez, Daniel GallegoRoy, SashwatiYoder, Mervin C.Sen, Chandan K.2023-11-022023-11-022023-02-28Pal D, Ghatak S, Singh K, et al. Identification of a physiologic vasculogenic fibroblast state to achieve tissue repair. Nat Commun. 2023;14(1):1129. Published 2023 Feb 28. doi:10.1038/s41467-023-36665-zhttps://hdl.handle.net/1805/36871Tissue 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.en-USAttribution 4.0 InternationalmiRNAsBioinformaticsGene deliveryIdentification of a physiologic vasculogenic fibroblast state to achieve tissue repairArticle