Single Cell Transcriptomic Landscape of Diabetic Foot Ulcers

Abstract

To understand the diabetic wound healing microenvironment, we profiled 174,962 single cells from foot, forearm, and PBMCs using single-cell RNA sequencing (scRNASeq) approach. Our analysis shows enrichment of a unique population of fibroblasts overexpressing MMP1, MMP3, MMP11, HIF1A, CHI3L1, and TNFAIP6 genes and M1 macrophage polarization in the DFU patients with healing wounds. Further, scRNASeq of spatially separated samples from same patient and spatial transcriptomics (ST) revealed preferential localization of these healing associated fibroblasts toward deep wound/ulcer bed as compared to wound edge or non-wounded skin. ST also validated our findings of higher enrichment of M1 macrophages in healers and M2 macrophages in non-healers. Our analysis provides deep insights into the wound healing microenvironment, identifying cell types that could be critical in promoting DFU healing, and may inform novel therapeutic approaches for DFU treatment.

Heterogeneity of Inflammation-associated Synovial Fibroblasts in Rheumatoid Arthritis and Its Drivers

“…Dot plot showing relative expression of selected gene signatures from published tissue fibroblast populations 11–14 in FLS clusters shown in Fig. 1a colored according to FLS states defined in Fig.…”

Strain-Programmable Patch for Diabetic Wound Healing

“…While the current work provides systematically investigated platform technology and proof-of-concept efficacy of the therapeutic potential, there are future steps to be taken for further investigation and clinical translation. Future investigations should focus on employing multi-omics methods to comprehensively map the different cell populations and signaling pathways influenced by the strain programmable-patch treatment (70,71). In addition, further studies are required to define applicability, frequency of application and suitable strain levels, among others, before use in a clinical setting.…”

Challenges and Opportunities for the Translation of Single-Cell RNA Sequencing Technologies to Dermatology

“…However, this work illustrated that extracting viable cells from the highly degraded tissue setting of a chronic ulcer may sometimes be challenging. Two recent preprints on single-cell-based characterization of DFUs and pressure ulcers seem to have overcome these limitations [90,91]. Theocharidis et al now analyze 94,325 cells from 26-foot samples from both healing and non-healing DFUs [90].…”

“…Two recent preprints on single-cell-based characterization of DFUs and pressure ulcers seem to have overcome these limitations [90,91]. Theocharidis et al now analyze 94,325 cells from 26-foot samples from both healing and non-healing DFUs [90]. They report that fibroblasts with the transcriptomic signature MMP1, MMP3, IL6, CHI3L1, ASPN, POSTN, PLA2G2A, and TNFAIP6 are associated with good DFU healers.…”