Analysis of immune cell activation in patients with diabetes foot ulcer from the perspective of single cell

Abstract Background Diabetes mellitus (DM) can cause severe complications, including diabetic foot ulcers (DFU). There is a significant gap in understanding the single-cell ecological atlas of DM and DFU tissues. Methods Single-cell RNA sequencing data were used to create a detailed single-cell ecol...

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Main Authors: Lehoanganh Vu, Fei Xu, Ting Li, Qikai Hua, Xiaocong Kuang, Yongqiang Jiang, Yanfei Liang, Xing Niu, Yixuan Chen, Chengyu Huang, Weiliang Mo, Kejian Wang, Kaihua Tang, Jianwen Mo, Ke-Er Lu, Yan Mo, Steven Mo, Dengfeng Yang, Jinmin Zhao
Format: Article
Language:English
Published: BMC 2024-12-01
Series:European Journal of Medical Research
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Online Access:https://doi.org/10.1186/s40001-024-02179-7
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author Lehoanganh Vu
Fei Xu
Ting Li
Qikai Hua
Xiaocong Kuang
Yongqiang Jiang
Yanfei Liang
Xing Niu
Yixuan Chen
Chengyu Huang
Weiliang Mo
Kejian Wang
Kaihua Tang
Jianwen Mo
Ke-Er Lu
Yan Mo
Steven Mo
Dengfeng Yang
Jinmin Zhao
author_facet Lehoanganh Vu
Fei Xu
Ting Li
Qikai Hua
Xiaocong Kuang
Yongqiang Jiang
Yanfei Liang
Xing Niu
Yixuan Chen
Chengyu Huang
Weiliang Mo
Kejian Wang
Kaihua Tang
Jianwen Mo
Ke-Er Lu
Yan Mo
Steven Mo
Dengfeng Yang
Jinmin Zhao
author_sort Lehoanganh Vu
collection DOAJ
description Abstract Background Diabetes mellitus (DM) can cause severe complications, including diabetic foot ulcers (DFU). There is a significant gap in understanding the single-cell ecological atlas of DM and DFU tissues. Methods Single-cell RNA sequencing data were used to create a detailed single-cell ecological landscape of DM and DFU. Enrichment analysis identified pathways involved in cellular subpopulations, and pseudo-time analysis inferred cell development processes. A gene regulatory network explored the role of transcription factors in DFU progression, and a potential herbal drug-target gene interaction network was constructed. Results In the DFU group, immune cells were activated, with notable changes in several subpopulations. ATP5E was significantly overexpressed in Naive T cells, fibroblasts, endothelial cells, and CD8+ T cells in DM patients. Specific immune cell subsets, such as Naive T_RGCC, CTL_TYROBP_CL4, Mac_SLC40A1, and M1_CCL3L1, likely contribute to DFU formation through overactivation and proliferation, leading to tissue damage and ulcer exacerbation. Key genes TPP1, TLR4, and RIPK2 were identified, and 88 active ingredients in the herbal drug-target network showed strong correlations with these targets. Herbs like Angelica dahurica, Angelica sinensis, Boswellia carterii, liquorice, myrrh, and Semen armeniacae amarae were included. Conclusions This study offers insights into DM and DFU cytology. T cells in DFU are activated, attacking normal tissues and worsening tissue damage. The ATP5E gene may be related to the ecological remodeling of DM, and TPP1, TLR4, and RIPK2 are potential targets for DFU treatment.
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spelling doaj-art-c9e259812eb54077b2e55f62db71e2a42025-08-20T02:32:01ZengBMCEuropean Journal of Medical Research2047-783X2024-12-0129111810.1186/s40001-024-02179-7Analysis of immune cell activation in patients with diabetes foot ulcer from the perspective of single cellLehoanganh Vu0Fei Xu1Ting Li2Qikai Hua3Xiaocong Kuang4Yongqiang Jiang5Yanfei Liang6Xing Niu7Yixuan Chen8Chengyu Huang9Weiliang Mo10Kejian Wang11Kaihua Tang12Jianwen Mo13Ke-Er Lu14Yan Mo15Steven Mo16Dengfeng Yang17Jinmin Zhao18Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical UniversitySystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesSystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesDepartment of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Physiology and Pathophysiology, Yulin Campus of Guangxi Medical UniversitySystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesSystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesSystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesSystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesSystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesSystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesSystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesSystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesSystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesSystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesDepartment of Pathology, Yulin Campus of Guangxi Medical UniversitySystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesSystems Biology Research Center, Biology Institute, Guangxi Academy of SciencesDepartment of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical UniversityAbstract Background Diabetes mellitus (DM) can cause severe complications, including diabetic foot ulcers (DFU). There is a significant gap in understanding the single-cell ecological atlas of DM and DFU tissues. Methods Single-cell RNA sequencing data were used to create a detailed single-cell ecological landscape of DM and DFU. Enrichment analysis identified pathways involved in cellular subpopulations, and pseudo-time analysis inferred cell development processes. A gene regulatory network explored the role of transcription factors in DFU progression, and a potential herbal drug-target gene interaction network was constructed. Results In the DFU group, immune cells were activated, with notable changes in several subpopulations. ATP5E was significantly overexpressed in Naive T cells, fibroblasts, endothelial cells, and CD8+ T cells in DM patients. Specific immune cell subsets, such as Naive T_RGCC, CTL_TYROBP_CL4, Mac_SLC40A1, and M1_CCL3L1, likely contribute to DFU formation through overactivation and proliferation, leading to tissue damage and ulcer exacerbation. Key genes TPP1, TLR4, and RIPK2 were identified, and 88 active ingredients in the herbal drug-target network showed strong correlations with these targets. Herbs like Angelica dahurica, Angelica sinensis, Boswellia carterii, liquorice, myrrh, and Semen armeniacae amarae were included. Conclusions This study offers insights into DM and DFU cytology. T cells in DFU are activated, attacking normal tissues and worsening tissue damage. The ATP5E gene may be related to the ecological remodeling of DM, and TPP1, TLR4, and RIPK2 are potential targets for DFU treatment.https://doi.org/10.1186/s40001-024-02179-7Diabetes mellitusDFUSingle-cell RNA sequencingApoptosisImmune activationDrug targets
spellingShingle Lehoanganh Vu
Fei Xu
Ting Li
Qikai Hua
Xiaocong Kuang
Yongqiang Jiang
Yanfei Liang
Xing Niu
Yixuan Chen
Chengyu Huang
Weiliang Mo
Kejian Wang
Kaihua Tang
Jianwen Mo
Ke-Er Lu
Yan Mo
Steven Mo
Dengfeng Yang
Jinmin Zhao
Analysis of immune cell activation in patients with diabetes foot ulcer from the perspective of single cell
European Journal of Medical Research
Diabetes mellitus
DFU
Single-cell RNA sequencing
Apoptosis
Immune activation
Drug targets
title Analysis of immune cell activation in patients with diabetes foot ulcer from the perspective of single cell
title_full Analysis of immune cell activation in patients with diabetes foot ulcer from the perspective of single cell
title_fullStr Analysis of immune cell activation in patients with diabetes foot ulcer from the perspective of single cell
title_full_unstemmed Analysis of immune cell activation in patients with diabetes foot ulcer from the perspective of single cell
title_short Analysis of immune cell activation in patients with diabetes foot ulcer from the perspective of single cell
title_sort analysis of immune cell activation in patients with diabetes foot ulcer from the perspective of single cell
topic Diabetes mellitus
DFU
Single-cell RNA sequencing
Apoptosis
Immune activation
Drug targets
url https://doi.org/10.1186/s40001-024-02179-7
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