Characterizing Fibroblast Heterogeneity in Diabetic Wounds Through Single-Cell RNA-Sequencing

Abstract

Diabetes mellitus is an increasingly prevalent chronic metabolic disorder characterized by physiologic hyperglycemia that, when left uncontrolled, can lead to significant complications in multiple organs. Diabetic wounds are common in the general population, yet the underlying mechanism of impaired healing in such wounds remains unclear. Single-cell RNA-sequencing (scRNAseq) has recently emerged as a tool to study the gene expression of heterogeneous cell populations in skin wounds. Herein, we review the history of scRNAseq and its application to the study of diabetic wound healing, focusing on how innovations in single-cell sequencing have transformed strategies for fibroblast analysis. We summarize recent research on the role of fibroblasts in diabetic wound healing and describe the functional and cellular heterogeneity of skin fibroblasts. Moreover, we highlight future opportunities in diabetic wound fibroblast research, with a focus on characterizing distinct fibroblast subpopulations and their lineages. Leveraging single-cell technologies to explore fibroblast heterogeneity and the complex biology of diabetic wounds may reveal new therapeutic targets for improving wound healing and ultimately alleviate the clinical burden of chronic wounds.

Keywords: diabetes; fibroblast; fibrosis; scRNAseq; single cell; transcriptomics; wound healing.

Figure 1

Illustrated Workflow for scRNAseq of Diabetic Wounds. An example workflow for single-cell RNA-seq of diabetic skin wounds using a droplet-based method such as 10x Genomics Chromium, from specimen harvest to downstream analysis of sequencing data. Optional cell sorting and in silico cell type isolation steps are illustrated using forked arrows. Created in BioRender. Wang, H. (2024) BioRender.com/p83k591 (accessed on 11 October 2024).