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 novel
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.
https://github.com/ChandanKSenLab/VF_Project/blob/main/VF_single-cell_analysis.md
Professor Chandan K. Sen, PhD
Indiana Center for Regenerative Medicine & Engineering, Department of Surgery,
Indiana University School of Medicine, Indianapolis, IN 46202
E-mail: cksen@iu.edu