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Single cell transcriptomic landscape of diabetic foot ulcers

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 Mezgha, 2022. "Single cell transcriptomic landscape of diabetic foot ulcers," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27801-8
    DOI: 10.1038/s41467-021-27801-8
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    Cited by:

    1. LiangYu Zhao & Sha Han & HengChuan Su & JianYing Li & ErLei Zhi & Peng Li & ChenCheng Yao & RuHui Tian & HuiXing Chen & HuiRong Chen & JiaQiang Luo & ChenKun Shi & ZhiYong Ji & JianLin Hu & Gang Wu & , 2022. "Single-cell transcriptome atlas of the human corpus cavernosum," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Yuanyuan Wei & Beidi Lan & Tao Zheng & Lin Yang & Xiaoxia Zhang & Lele Cheng & Gulinigaer Tuerhongjiang & Zuyi Yuan & Yue Wu, 2023. "GSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Nancy Yanzhe Li & Weiruo Zhang & Daniel Haensel & Anna R. Jussila & Cory Pan & Sadhana Gaddam & Sylvia K. Plevritis & Anthony E. Oro, 2024. "Basal-to-inflammatory transition and tumor resistance via crosstalk with a pro-inflammatory stromal niche," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    4. Xueyan Wu & Hui Ying & Qianqian Yang & Qian Yang & Haoyu Liu & Yilan Ding & Huiling Zhao & Zhihe Chen & Ruizhi Zheng & Hong Lin & Shuangyuan Wang & Mian Li & Tiange Wang & Zhiyun Zhao & Min Xu & Yuhon, 2024. "Transcriptome-wide Mendelian randomization during CD4+ T cell activation reveals immune-related drug targets for cardiometabolic diseases," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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