Single-cell RNA sequencing reveals a new mechanism of endothelial cell heterogeneity and healing in diabetic foot ulcers

Abstract Diabetic foot ulcers (DFU) are a common and severe complication among diabetic patients, posing a significant burden on patients’ quality of life and healthcare systems due to their high incidence, amputation rates, and mortality. This study utilized single-cell RNA sequencing technology to...

Full description

Saved in:
Bibliographic Details
Main Authors: Songyun Zhao, Hua Yu, Zihao Li, Wanying Chen, Kaibo Liu, Hao Dai, Gaoyi Wang, Zibing Zhang, Jiaheng Xie, Yucang He, Liqun Li
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Biology Direct
Subjects:
Online Access:https://doi.org/10.1186/s13062-025-00628-9
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849390355207684096
author Songyun Zhao
Hua Yu
Zihao Li
Wanying Chen
Kaibo Liu
Hao Dai
Gaoyi Wang
Zibing Zhang
Jiaheng Xie
Yucang He
Liqun Li
author_facet Songyun Zhao
Hua Yu
Zihao Li
Wanying Chen
Kaibo Liu
Hao Dai
Gaoyi Wang
Zibing Zhang
Jiaheng Xie
Yucang He
Liqun Li
author_sort Songyun Zhao
collection DOAJ
description Abstract Diabetic foot ulcers (DFU) are a common and severe complication among diabetic patients, posing a significant burden on patients’ quality of life and healthcare systems due to their high incidence, amputation rates, and mortality. This study utilized single-cell RNA sequencing technology to deeply analyze the cellular heterogeneity of the skin on the feet ofDFU patients and the transcriptomic characteristics of endothelial cells, aiming to identify key cell populations and genes associated with the healing and progression of DFU. The study found that endothelial cells from DFU patients exhibited significant transcriptomic differences under various conditions, particularly in signaling pathways related to inflammatory responses and angiogenesis. Through trajectory analysis and cell communication research, we revealed the key role of endothelial cell subsets in the development of DFU and identified multiple important gene modules associated with the progression of DFU. Notably, the promoting effect of the SH3BGRL3 gene on endothelial cell proliferation, migration, and angiogenic capabilities under high glucose conditions was experimentally verified, providing a new potential target and theoretical basis for the treatment of DFU. This study not only enhances the understanding of the pathogenesis ofDFU but also provides a scientific basis for the development ofnew therapeutic strategies.
format Article
id doaj-art-5857e7cf3e254e949362e723f0a9ba45
institution Kabale University
issn 1745-6150
language English
publishDate 2025-03-01
publisher BMC
record_format Article
series Biology Direct
spelling doaj-art-5857e7cf3e254e949362e723f0a9ba452025-08-20T03:41:41ZengBMCBiology Direct1745-61502025-03-0120112110.1186/s13062-025-00628-9Single-cell RNA sequencing reveals a new mechanism of endothelial cell heterogeneity and healing in diabetic foot ulcersSongyun Zhao0Hua Yu1Zihao Li2Wanying Chen3Kaibo Liu4Hao Dai5Gaoyi Wang6Zibing Zhang7Jiaheng Xie8Yucang He9Liqun Li10Department of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Plastic Surgery, Xiangya Hospital, Central South UniversityDepartment of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical UniversityAbstract Diabetic foot ulcers (DFU) are a common and severe complication among diabetic patients, posing a significant burden on patients’ quality of life and healthcare systems due to their high incidence, amputation rates, and mortality. This study utilized single-cell RNA sequencing technology to deeply analyze the cellular heterogeneity of the skin on the feet ofDFU patients and the transcriptomic characteristics of endothelial cells, aiming to identify key cell populations and genes associated with the healing and progression of DFU. The study found that endothelial cells from DFU patients exhibited significant transcriptomic differences under various conditions, particularly in signaling pathways related to inflammatory responses and angiogenesis. Through trajectory analysis and cell communication research, we revealed the key role of endothelial cell subsets in the development of DFU and identified multiple important gene modules associated with the progression of DFU. Notably, the promoting effect of the SH3BGRL3 gene on endothelial cell proliferation, migration, and angiogenic capabilities under high glucose conditions was experimentally verified, providing a new potential target and theoretical basis for the treatment of DFU. This study not only enhances the understanding of the pathogenesis ofDFU but also provides a scientific basis for the development ofnew therapeutic strategies.https://doi.org/10.1186/s13062-025-00628-9Diabetic foot ulcersSingle-cell RNA sequencingEndothelial cellsSH3BGRL3Wound healingAngiogenesis
spellingShingle Songyun Zhao
Hua Yu
Zihao Li
Wanying Chen
Kaibo Liu
Hao Dai
Gaoyi Wang
Zibing Zhang
Jiaheng Xie
Yucang He
Liqun Li
Single-cell RNA sequencing reveals a new mechanism of endothelial cell heterogeneity and healing in diabetic foot ulcers
Biology Direct
Diabetic foot ulcers
Single-cell RNA sequencing
Endothelial cells
SH3BGRL3
Wound healing
Angiogenesis
title Single-cell RNA sequencing reveals a new mechanism of endothelial cell heterogeneity and healing in diabetic foot ulcers
title_full Single-cell RNA sequencing reveals a new mechanism of endothelial cell heterogeneity and healing in diabetic foot ulcers
title_fullStr Single-cell RNA sequencing reveals a new mechanism of endothelial cell heterogeneity and healing in diabetic foot ulcers
title_full_unstemmed Single-cell RNA sequencing reveals a new mechanism of endothelial cell heterogeneity and healing in diabetic foot ulcers
title_short Single-cell RNA sequencing reveals a new mechanism of endothelial cell heterogeneity and healing in diabetic foot ulcers
title_sort single cell rna sequencing reveals a new mechanism of endothelial cell heterogeneity and healing in diabetic foot ulcers
topic Diabetic foot ulcers
Single-cell RNA sequencing
Endothelial cells
SH3BGRL3
Wound healing
Angiogenesis
url https://doi.org/10.1186/s13062-025-00628-9
work_keys_str_mv AT songyunzhao singlecellrnasequencingrevealsanewmechanismofendothelialcellheterogeneityandhealingindiabeticfootulcers
AT huayu singlecellrnasequencingrevealsanewmechanismofendothelialcellheterogeneityandhealingindiabeticfootulcers
AT zihaoli singlecellrnasequencingrevealsanewmechanismofendothelialcellheterogeneityandhealingindiabeticfootulcers
AT wanyingchen singlecellrnasequencingrevealsanewmechanismofendothelialcellheterogeneityandhealingindiabeticfootulcers
AT kaiboliu singlecellrnasequencingrevealsanewmechanismofendothelialcellheterogeneityandhealingindiabeticfootulcers
AT haodai singlecellrnasequencingrevealsanewmechanismofendothelialcellheterogeneityandhealingindiabeticfootulcers
AT gaoyiwang singlecellrnasequencingrevealsanewmechanismofendothelialcellheterogeneityandhealingindiabeticfootulcers
AT zibingzhang singlecellrnasequencingrevealsanewmechanismofendothelialcellheterogeneityandhealingindiabeticfootulcers
AT jiahengxie singlecellrnasequencingrevealsanewmechanismofendothelialcellheterogeneityandhealingindiabeticfootulcers
AT yucanghe singlecellrnasequencingrevealsanewmechanismofendothelialcellheterogeneityandhealingindiabeticfootulcers
AT liqunli singlecellrnasequencingrevealsanewmechanismofendothelialcellheterogeneityandhealingindiabeticfootulcers