Single-cell transcriptome profiling highlights the role of APP in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing Alzheimer’s disease

Introduction: The incidence of diabetic retinopathy (DR) has been found to be associated with the risk of developing Alzheimer‘s disease (AD). In addition to the common properties of neurodegeneration, their progressions are involved with abnormal vascular functions. However, the interactions betwee...

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Main Authors: Xiaoyu Xu, Cheng Zhang, Guoyi Tang, Ning Wang, Yibin Feng
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2023.1328979/full
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author Xiaoyu Xu
Cheng Zhang
Guoyi Tang
Ning Wang
Yibin Feng
author_facet Xiaoyu Xu
Cheng Zhang
Guoyi Tang
Ning Wang
Yibin Feng
author_sort Xiaoyu Xu
collection DOAJ
description Introduction: The incidence of diabetic retinopathy (DR) has been found to be associated with the risk of developing Alzheimer‘s disease (AD). In addition to the common properties of neurodegeneration, their progressions are involved with abnormal vascular functions. However, the interactions between them have not been fully understood. This study aimed to investigate the key factor for the underlying interactions and shared signaling pathways in the vasculature of DR and AD.Methods: We retrieved single-cell RNA sequencing (scRNA-seq) data regarding human fibrovascular membrane (FVM) of proliferative diabetic retinopathy (PDR) and human hippocampus vessels of AD from the NCBI-GEO database. GSEA analysis was performed to analyze AD-related genes in endothelial cells and pericytes of PDR. CellChat was used for predicting cell-cell communication and the signaling pathway.Results: The data suggested that amyloid-beta precursor protein (APP) signaling was found crucial in the vasculature of PDR and AD. Endothelial cells and pericytes could pose influences on other cells mainly via APP signaling in PDR. The endothelial cells were mainly coordinated with macrophages in the hippocampus vasculature of AD via APP signaling. The bulk RNA-seq in mice with PDR validated that the expression of APP gene had a significant correlation with that of the AD genome-wide association studies (GWAS) gene.Discussion: Our study demonstrates that the vasculopathy of PDR and AD is likely to share a common signaling pathway, of which the APP-related pathway is a potential target.
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spelling doaj.art-d2ff14ae7dea4da29a1c91532855afb42024-01-24T04:30:39ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2024-01-011110.3389/fcell.2023.13289791328979Single-cell transcriptome profiling highlights the role of APP in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing Alzheimer’s diseaseXiaoyu XuCheng ZhangGuoyi TangNing WangYibin FengIntroduction: The incidence of diabetic retinopathy (DR) has been found to be associated with the risk of developing Alzheimer‘s disease (AD). In addition to the common properties of neurodegeneration, their progressions are involved with abnormal vascular functions. However, the interactions between them have not been fully understood. This study aimed to investigate the key factor for the underlying interactions and shared signaling pathways in the vasculature of DR and AD.Methods: We retrieved single-cell RNA sequencing (scRNA-seq) data regarding human fibrovascular membrane (FVM) of proliferative diabetic retinopathy (PDR) and human hippocampus vessels of AD from the NCBI-GEO database. GSEA analysis was performed to analyze AD-related genes in endothelial cells and pericytes of PDR. CellChat was used for predicting cell-cell communication and the signaling pathway.Results: The data suggested that amyloid-beta precursor protein (APP) signaling was found crucial in the vasculature of PDR and AD. Endothelial cells and pericytes could pose influences on other cells mainly via APP signaling in PDR. The endothelial cells were mainly coordinated with macrophages in the hippocampus vasculature of AD via APP signaling. The bulk RNA-seq in mice with PDR validated that the expression of APP gene had a significant correlation with that of the AD genome-wide association studies (GWAS) gene.Discussion: Our study demonstrates that the vasculopathy of PDR and AD is likely to share a common signaling pathway, of which the APP-related pathway is a potential target.https://www.frontiersin.org/articles/10.3389/fcell.2023.1328979/fullproliferative diabetic retinopathyAlzheimer’s diseasevasculatureamyloid-beta precursor proteinendothelial cells
spellingShingle Xiaoyu Xu
Cheng Zhang
Guoyi Tang
Ning Wang
Yibin Feng
Single-cell transcriptome profiling highlights the role of APP in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing Alzheimer’s disease
Frontiers in Cell and Developmental Biology
proliferative diabetic retinopathy
Alzheimer’s disease
vasculature
amyloid-beta precursor protein
endothelial cells
title Single-cell transcriptome profiling highlights the role of APP in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing Alzheimer’s disease
title_full Single-cell transcriptome profiling highlights the role of APP in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing Alzheimer’s disease
title_fullStr Single-cell transcriptome profiling highlights the role of APP in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing Alzheimer’s disease
title_full_unstemmed Single-cell transcriptome profiling highlights the role of APP in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing Alzheimer’s disease
title_short Single-cell transcriptome profiling highlights the role of APP in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing Alzheimer’s disease
title_sort single cell transcriptome profiling highlights the role of app in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing alzheimer s disease
topic proliferative diabetic retinopathy
Alzheimer’s disease
vasculature
amyloid-beta precursor protein
endothelial cells
url https://www.frontiersin.org/articles/10.3389/fcell.2023.1328979/full
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