Identification of podocyte molecular markers in diabetic kidney disease via single-cell RNA sequencing and machine learning.

Diabetic kidney disease (DKD) is a major cause of end-stage renal disease globally, with podocytes being implicated in its pathogenesis. However, the underlying mechanisms of podocyte involvement remain unclear. The aim of the present study was to identify podocyte molecular markers associated with...

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Main Authors: Hailin Li, Quhuan Li, Zuyan Fan, Yue Shen, Jiao Li, Fengxia Zhang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0328352
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author Hailin Li
Quhuan Li
Zuyan Fan
Yue Shen
Jiao Li
Fengxia Zhang
author_facet Hailin Li
Quhuan Li
Zuyan Fan
Yue Shen
Jiao Li
Fengxia Zhang
author_sort Hailin Li
collection DOAJ
description Diabetic kidney disease (DKD) is a major cause of end-stage renal disease globally, with podocytes being implicated in its pathogenesis. However, the underlying mechanisms of podocyte involvement remain unclear. The aim of the present study was to identify podocyte molecular markers associated with DKD using single-cell RNA sequencing (scRNA-seq) data from patients with early DKD. Through enrichment analysis, subcluster clustering, and ligand-receptor (LR) interaction analysis, we elucidated the role of podocytes in early DKD progression. Podocyte heterogeneity and functional differences in DKD were observed. Multiple machine-learning algorithms were used to screen and construct diagnostic models to identify hub differentially expressed podocyte marker genes (DE-podos), revealing ARHGEF26 as a significantly downregulated marker in DKD. Validation using external datasets, reverse transcription quantitative real-time PCR (RT-qPCR) and Western blot confirmed it as a potential diagnostic biomarker. Our findings elucidate podocyte function in DKD and provide viable therapeutic targets, potentially improving diagnostic accuracy and treatment outcomes.
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publisher Public Library of Science (PLoS)
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series PLoS ONE
spelling doaj-art-c879101c76c24d8a98649ced6f931f062025-08-20T03:13:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01207e032835210.1371/journal.pone.0328352Identification of podocyte molecular markers in diabetic kidney disease via single-cell RNA sequencing and machine learning.Hailin LiQuhuan LiZuyan FanYue ShenJiao LiFengxia ZhangDiabetic kidney disease (DKD) is a major cause of end-stage renal disease globally, with podocytes being implicated in its pathogenesis. However, the underlying mechanisms of podocyte involvement remain unclear. The aim of the present study was to identify podocyte molecular markers associated with DKD using single-cell RNA sequencing (scRNA-seq) data from patients with early DKD. Through enrichment analysis, subcluster clustering, and ligand-receptor (LR) interaction analysis, we elucidated the role of podocytes in early DKD progression. Podocyte heterogeneity and functional differences in DKD were observed. Multiple machine-learning algorithms were used to screen and construct diagnostic models to identify hub differentially expressed podocyte marker genes (DE-podos), revealing ARHGEF26 as a significantly downregulated marker in DKD. Validation using external datasets, reverse transcription quantitative real-time PCR (RT-qPCR) and Western blot confirmed it as a potential diagnostic biomarker. Our findings elucidate podocyte function in DKD and provide viable therapeutic targets, potentially improving diagnostic accuracy and treatment outcomes.https://doi.org/10.1371/journal.pone.0328352
spellingShingle Hailin Li
Quhuan Li
Zuyan Fan
Yue Shen
Jiao Li
Fengxia Zhang
Identification of podocyte molecular markers in diabetic kidney disease via single-cell RNA sequencing and machine learning.
PLoS ONE
title Identification of podocyte molecular markers in diabetic kidney disease via single-cell RNA sequencing and machine learning.
title_full Identification of podocyte molecular markers in diabetic kidney disease via single-cell RNA sequencing and machine learning.
title_fullStr Identification of podocyte molecular markers in diabetic kidney disease via single-cell RNA sequencing and machine learning.
title_full_unstemmed Identification of podocyte molecular markers in diabetic kidney disease via single-cell RNA sequencing and machine learning.
title_short Identification of podocyte molecular markers in diabetic kidney disease via single-cell RNA sequencing and machine learning.
title_sort identification of podocyte molecular markers in diabetic kidney disease via single cell rna sequencing and machine learning
url https://doi.org/10.1371/journal.pone.0328352
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