Cell Atlas of The Human Fovea and Peripheral Retina

© 2020, The Author(s). Most irreversible blindness results from retinal disease. To advance our understanding of the etiology of blinding diseases, we used single-cell RNA-sequencing (scRNA-seq) to analyze the transcriptomes of ~85,000 cells from the fovea and peripheral retina of seven adult human...

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Main Authors: Yan, Wenjun, Peng, Yi-Rong, van Zyl, Tavé, Regev, Aviv, Shekhar, Karthik, Juric, Dejan, Sanes, Joshua R
Other Authors: Howard Hughes Medical Institute
Format: Article
Language:English
Published: Springer Science and Business Media LLC 2021
Online Access:https://hdl.handle.net/1721.1/135412
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author Yan, Wenjun
Peng, Yi-Rong
van Zyl, Tavé
Regev, Aviv
Shekhar, Karthik
Juric, Dejan
Sanes, Joshua R
author2 Howard Hughes Medical Institute
author_facet Howard Hughes Medical Institute
Yan, Wenjun
Peng, Yi-Rong
van Zyl, Tavé
Regev, Aviv
Shekhar, Karthik
Juric, Dejan
Sanes, Joshua R
author_sort Yan, Wenjun
collection MIT
description © 2020, The Author(s). Most irreversible blindness results from retinal disease. To advance our understanding of the etiology of blinding diseases, we used single-cell RNA-sequencing (scRNA-seq) to analyze the transcriptomes of ~85,000 cells from the fovea and peripheral retina of seven adult human donors. Utilizing computational methods, we identified 58 cell types within 6 classes: photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and non-neuronal cells. Nearly all types are shared between the two retinal regions, but there are notable differences in gene expression and proportions between foveal and peripheral cohorts of shared types. We then used the human retinal atlas to map expression of 636 genes implicated as causes of or risk factors for blinding diseases. Many are expressed in striking cell class-, type-, or region-specific patterns. Finally, we compared gene expression signatures of cell types between human and the cynomolgus macaque monkey, Macaca fascicularis. We show that over 90% of human types correspond transcriptomically to those previously identified in macaque, and that expression of disease-related genes is largely conserved between the two species. These results validate the use of the macaque for modeling blinding disease, and provide a foundation for investigating molecular mechanisms underlying visual processing.
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spelling mit-1721.1/1354122023-10-06T20:33:34Z Cell Atlas of The Human Fovea and Peripheral Retina Yan, Wenjun Peng, Yi-Rong van Zyl, Tavé Regev, Aviv Shekhar, Karthik Juric, Dejan Sanes, Joshua R Howard Hughes Medical Institute Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Department of Biology © 2020, The Author(s). Most irreversible blindness results from retinal disease. To advance our understanding of the etiology of blinding diseases, we used single-cell RNA-sequencing (scRNA-seq) to analyze the transcriptomes of ~85,000 cells from the fovea and peripheral retina of seven adult human donors. Utilizing computational methods, we identified 58 cell types within 6 classes: photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and non-neuronal cells. Nearly all types are shared between the two retinal regions, but there are notable differences in gene expression and proportions between foveal and peripheral cohorts of shared types. We then used the human retinal atlas to map expression of 636 genes implicated as causes of or risk factors for blinding diseases. Many are expressed in striking cell class-, type-, or region-specific patterns. Finally, we compared gene expression signatures of cell types between human and the cynomolgus macaque monkey, Macaca fascicularis. We show that over 90% of human types correspond transcriptomically to those previously identified in macaque, and that expression of disease-related genes is largely conserved between the two species. These results validate the use of the macaque for modeling blinding disease, and provide a foundation for investigating molecular mechanisms underlying visual processing. 2021-10-27T20:23:22Z 2021-10-27T20:23:22Z 2020 2021-07-22T16:27:29Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135412 en 10.1038/S41598-020-66092-9 Scientific Reports Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Scientific Reports
spellingShingle Yan, Wenjun
Peng, Yi-Rong
van Zyl, Tavé
Regev, Aviv
Shekhar, Karthik
Juric, Dejan
Sanes, Joshua R
Cell Atlas of The Human Fovea and Peripheral Retina
title Cell Atlas of The Human Fovea and Peripheral Retina
title_full Cell Atlas of The Human Fovea and Peripheral Retina
title_fullStr Cell Atlas of The Human Fovea and Peripheral Retina
title_full_unstemmed Cell Atlas of The Human Fovea and Peripheral Retina
title_short Cell Atlas of The Human Fovea and Peripheral Retina
title_sort cell atlas of the human fovea and peripheral retina
url https://hdl.handle.net/1721.1/135412
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