Single cell transcriptomic landscape of diabetic foot ulcers

Georgios Theocharidis, Beena E. Thomas, Debasree Sarkar, Hope L. Mumme, William J. R. Pilcher, Bhakti Dwivedi, Teresa Sandoval-Schaefer, Ruxandra F. Sîrbulescu, Antonios Kafanas, Ikram Mezghani, Peng Wang, Antonio Lobao, Ioannis S. Vlachos, Biraja Dash, Henry C. Hsia, Valerie Horsley, Swati S. Bhasin, Aristidis Veves () and Manoj Bhasin ()
Additional contact information
Georgios Theocharidis: Beth Israel Deaconess Medical Center and Harvard Medical School
Beena E. Thomas: Emory University
Debasree Sarkar: Emory University
Hope L. Mumme: Emory University
William J. R. Pilcher: Emory University
Bhakti Dwivedi: Emory University
Teresa Sandoval-Schaefer: Yale University
Ruxandra F. Sîrbulescu: Harvard Medical School
Antonios Kafanas: Northern Lincolnshire and Goole NHS Foundation Trust
Ikram Mezghani: Beth Israel Deaconess Medical Center and Harvard Medical School
Peng Wang: Beth Israel Deaconess Medical Center and Harvard Medical School
Antonio Lobao: Beth Israel Deaconess Medical Center and Harvard Medical School
Ioannis S. Vlachos: Beth Israel Deaconess Medical Center, and Harvard Medical School
Biraja Dash: Yale School of Medicine
Henry C. Hsia: Yale School of Medicine
Valerie Horsley: Yale University
Swati S. Bhasin: Emory University
Aristidis Veves: Beth Israel Deaconess Medical Center and Harvard Medical School
Manoj Bhasin: Emory University

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-021-27801-8

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