Implication of specific retinal cell-type involvement and gene expression changes in AMD progression using integrative analysis of single-cell and bulk RNA-seq profiling

Abstract Age‐related macular degeneration (AMD) is a blinding eye disease with no unifying theme for its etiology. We used single-cell RNA sequencing to analyze the transcriptomes of ~ 93,000 cells from the macula and peripheral retina from two adult human donors and bulk RNA sequencing from fifteen...

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Autores principales:	Yafei Lyu, Randy Zauhar, Nicholas Dana, Christianne E. Strang, Jian Hu, Kui Wang, Shanrun Liu, Naifei Pan, Paul Gamlin, James A. Kimble, Jeffrey D. Messinger, Christine A. Curcio, Dwight Stambolian, Mingyao Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1fb14e76067840689b61cd1fd4222f8f
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spelling	oai:doaj.org-article:1fb14e76067840689b61cd1fd4222f8f2021-12-02T14:53:42ZImplication of specific retinal cell-type involvement and gene expression changes in AMD progression using integrative analysis of single-cell and bulk RNA-seq profiling10.1038/s41598-021-95122-32045-2322https://doaj.org/article/1fb14e76067840689b61cd1fd4222f8f2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95122-3https://doaj.org/toc/2045-2322Abstract Age‐related macular degeneration (AMD) is a blinding eye disease with no unifying theme for its etiology. We used single-cell RNA sequencing to analyze the transcriptomes of ~ 93,000 cells from the macula and peripheral retina from two adult human donors and bulk RNA sequencing from fifteen adult human donors with and without AMD. Analysis of our single-cell data identified 267 cell-type-specific genes. Comparison of macula and peripheral retinal regions found no cell-type differences but did identify 50 differentially expressed genes (DEGs) with about 1/3 expressed in cones. Integration of our single-cell data with bulk RNA sequencing data from normal and AMD donors showed compositional changes more pronounced in macula in rods, microglia, endothelium, Müller glia, and astrocytes in the transition from normal to advanced AMD. KEGG pathway analysis of our normal vs. advanced AMD eyes identified enrichment in complement and coagulation pathways, antigen presentation, tissue remodeling, and signaling pathways including PI3K-Akt, NOD-like, Toll-like, and Rap1. These results showcase the use of single-cell RNA sequencing to infer cell-type compositional and cell-type-specific gene expression changes in intact bulk tissue and provide a foundation for investigating molecular mechanisms of retinal disease that lead to new therapeutic targets.Yafei LyuRandy ZauharNicholas DanaChristianne E. StrangJian HuKui WangShanrun LiuNaifei PanPaul GamlinJames A. KimbleJeffrey D. MessingerChristine A. CurcioDwight StambolianMingyao LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yafei Lyu Randy Zauhar Nicholas Dana Christianne E. Strang Jian Hu Kui Wang Shanrun Liu Naifei Pan Paul Gamlin James A. Kimble Jeffrey D. Messinger Christine A. Curcio Dwight Stambolian Mingyao Li Implication of specific retinal cell-type involvement and gene expression changes in AMD progression using integrative analysis of single-cell and bulk RNA-seq profiling
description	Abstract Age‐related macular degeneration (AMD) is a blinding eye disease with no unifying theme for its etiology. We used single-cell RNA sequencing to analyze the transcriptomes of ~ 93,000 cells from the macula and peripheral retina from two adult human donors and bulk RNA sequencing from fifteen adult human donors with and without AMD. Analysis of our single-cell data identified 267 cell-type-specific genes. Comparison of macula and peripheral retinal regions found no cell-type differences but did identify 50 differentially expressed genes (DEGs) with about 1/3 expressed in cones. Integration of our single-cell data with bulk RNA sequencing data from normal and AMD donors showed compositional changes more pronounced in macula in rods, microglia, endothelium, Müller glia, and astrocytes in the transition from normal to advanced AMD. KEGG pathway analysis of our normal vs. advanced AMD eyes identified enrichment in complement and coagulation pathways, antigen presentation, tissue remodeling, and signaling pathways including PI3K-Akt, NOD-like, Toll-like, and Rap1. These results showcase the use of single-cell RNA sequencing to infer cell-type compositional and cell-type-specific gene expression changes in intact bulk tissue and provide a foundation for investigating molecular mechanisms of retinal disease that lead to new therapeutic targets.
format	article
author	Yafei Lyu Randy Zauhar Nicholas Dana Christianne E. Strang Jian Hu Kui Wang Shanrun Liu Naifei Pan Paul Gamlin James A. Kimble Jeffrey D. Messinger Christine A. Curcio Dwight Stambolian Mingyao Li
author_facet	Yafei Lyu Randy Zauhar Nicholas Dana Christianne E. Strang Jian Hu Kui Wang Shanrun Liu Naifei Pan Paul Gamlin James A. Kimble Jeffrey D. Messinger Christine A. Curcio Dwight Stambolian Mingyao Li
author_sort	Yafei Lyu
title	Implication of specific retinal cell-type involvement and gene expression changes in AMD progression using integrative analysis of single-cell and bulk RNA-seq profiling
title_short	Implication of specific retinal cell-type involvement and gene expression changes in AMD progression using integrative analysis of single-cell and bulk RNA-seq profiling
title_full	Implication of specific retinal cell-type involvement and gene expression changes in AMD progression using integrative analysis of single-cell and bulk RNA-seq profiling
title_fullStr	Implication of specific retinal cell-type involvement and gene expression changes in AMD progression using integrative analysis of single-cell and bulk RNA-seq profiling
title_full_unstemmed	Implication of specific retinal cell-type involvement and gene expression changes in AMD progression using integrative analysis of single-cell and bulk RNA-seq profiling
title_sort	implication of specific retinal cell-type involvement and gene expression changes in amd progression using integrative analysis of single-cell and bulk rna-seq profiling
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1fb14e76067840689b61cd1fd4222f8f
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Implication of specific retinal cell-type involvement and gene expression changes in AMD progression using integrative analysis of single-cell and bulk RNA-seq profiling

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