Frontiers in Endocrinology (Dec 2023)
Single-cell profiling reveals transcriptomic signatures of vascular endothelial cells in non-healing diabetic foot ulcers
- Yangzhou Lu,
- Yangzhou Lu,
- Yangzhou Lu,
- Xiaogang Liu,
- Xiaogang Liu,
- Xiaogang Liu,
- Jingling Zhao,
- Jingling Zhao,
- Jingling Zhao,
- Fan Bie,
- Fan Bie,
- Fan Bie,
- Yiling Liu,
- Yiling Liu,
- Yiling Liu,
- Julin Xie,
- Julin Xie,
- Julin Xie,
- Peng Wang,
- Peng Wang,
- Peng Wang,
- Junyou Zhu,
- Junyou Zhu,
- Junyou Zhu,
- Yahui Xiong,
- Yahui Xiong,
- Yahui Xiong,
- Shitian Qin,
- Shitian Qin,
- Shitian Qin,
- Fan Yang,
- Fan Yang,
- Fan Yang,
- Lei Chen,
- Lei Chen,
- Lei Chen,
- Yingbin Xu,
- Yingbin Xu,
- Yingbin Xu
Affiliations
- Yangzhou Lu
- Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Yangzhou Lu
- Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Yangzhou Lu
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Xiaogang Liu
- Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Xiaogang Liu
- Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Xiaogang Liu
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Jingling Zhao
- Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Jingling Zhao
- Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Jingling Zhao
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Fan Bie
- Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Fan Bie
- Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Fan Bie
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Yiling Liu
- Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Yiling Liu
- Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Yiling Liu
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Julin Xie
- Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Julin Xie
- Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Julin Xie
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Peng Wang
- Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Peng Wang
- Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Peng Wang
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Junyou Zhu
- Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Junyou Zhu
- Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Junyou Zhu
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Yahui Xiong
- Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Yahui Xiong
- Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Yahui Xiong
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Shitian Qin
- Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Shitian Qin
- Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Shitian Qin
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Fan Yang
- Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Fan Yang
- Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Fan Yang
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Lei Chen
- Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Lei Chen
- Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Lei Chen
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Yingbin Xu
- Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Yingbin Xu
- Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Yingbin Xu
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- DOI
- https://doi.org/10.3389/fendo.2023.1275612
- Journal volume & issue
-
Vol. 14
Abstract
BackgroundThe treatment of diabetic foot ulcers (DFUs) poses a challenging medical problem that has long plagued individuals with diabetes. Clinically, wounds that fail to heal for more than 12 weeks after the formation of DFUs are referred to as non-healing/chronic wounds. Among various factors contributing to the non-healing of DFUs, the impairment of skin microvascular endothelial cell function caused by high glucose plays a crucial role. Our study aimed to reveal the transcriptomic signatures of non-healing DFUs endothelial cells, providing novel intervention targets for treatment strategies.MethodsBased on the GEO dataset (GSE165816), we selected DFU-Healer, DFU-Non-healer, and healthy non-diabetic controls as research subjects. Single-cell RNA transcriptomic sequencing technology was employed to analyze the heterogeneity of endothelial cells in different skin tissue samples and identify healing-related endothelial cell subpopulations. Immunofluorescence was applied to validate the sequencing results on clinical specimens.ResultsThe number of endothelial cells and vascular density showed no significant differences among the three groups of skin specimens. However, endothelial cells from non-healing DFUs exhibited apparent inhibition of angiogenesis, inflammation, and immune-related signaling pathways. The expression of CCND1, ENO1, HIF1α, and SERPINE1 was significantly downregulated at the transcriptomic and histological levels. Further analysis demonstrated that healing-related endothelial cell subpopulations in non-healing DFUs has limited connection with other cell types and weaker differentiation ability.ConclusionAt the single-cell level, we uncovered the molecular and functional specificity of endothelial cells in non-healing DFUs and highlighted the importance of endothelial cell immune-mediated capability in angiogenesis and wound healing. This provides new insights for the treatment of DFUs.
Keywords
- single-cell RNA sequencing
- diabetic foot ulcers
- non-healing wounds
- vascular endothelial cell
- immune
- inflammation
