Diabetic foot ulcers (DFUs) are a devastating complication of diabetes. In order to identify systemic and local factors associated with DFU healing, we examined the cellular landscape of DFUs by single-cell RNA-seq analysis of foot and forearm skin specimens, as well as PBMC samples, from 10 non-diabetic subjects, and 17 diabetic patients, 11 with, and 6 without DFU. Our analysis shows enrichment of a unique inflammatory fibroblast population in DFU patients with healing wounds. The patients with healing DFUs also depicted enrichment of macrophages with M1 polarization, as opposed to more M2 macrophages in non-healing wounds. These findings were verified using Immunohistochemistry and Spatial Transcriptomics.

Study Overview: UMAP embedding of the scRNA-seq dataset consisting of 175,552 cells from foot, forearm and peripheral blood of 17 Diabetic subjects, 11 with and 6 without foot ulcers, and 10 healthy non-diabteics as control, colored by orthogonally generated clusters, and labeled by manual cell type annotation.

Table 1: Distribution of different cell types (Average % of cells ± SE) across anatomical locations

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Control

DFU-Healer

DFU-Nonhealer

Diabetic

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Single Cell Transcriptomic Landscape of Diabetic Foot Ulcers

Table 1: Distribution of different cell types (Average % of cells ± SE) across anatomical locations