Single cell transcriptomic landscape of diabetic foot ulcers.
Authors Theocharidis G, Thomas BE, Sarkar D, Mumme HL, Pilcher WJR, Dwivedi B,
Sandoval-Schaefer T, Sîrbulescu RF, Kafanas A, Mezghani I, Wang P, Lobao A,
Vlachos IS, Dash B, Hsia HC, Horsley V, Bhasin SS, Veves A, Bhasin M
Submitted By Aristidis Veves on 10/16/2023
Status Published
Journal Nature communications
Year 2022
Date Published 1/10/2022
Volume : Pages 13 : 181
PubMed Reference 35013299
Abstract Diabetic foot ulceration (DFU) is a devastating complication of diabetes whose
pathogenesis remains incompletely understood. Here, we profile 174,962 single
cells from the foot, forearm, and peripheral blood mononuclear cells using
single-cell RNA sequencing. Our analysis shows enrichment of a unique population
of fibroblasts overexpressing MMP1, MMP3, MMP11, HIF1A, CHI3L1, and TNFAIP6 and
increased M1 macrophage polarization in the DFU patients with healing wounds.
Further, analysis of spatially separated samples from the same patient and
spatial transcriptomics reveal preferential localization of these healing
associated fibroblasts toward the wound bed as compared to the wound edge or
unwounded skin. Spatial transcriptomics also validates our findings of higher
abundance 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.


Investigators with authorship
NameInstitution
Valerie HorsleyYale University
Aristidis VevesBeth Israel Deaconess Medical

Complications