Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution.
Cell Culture Techniques
/ methods
Cell Differentiation
/ genetics
Cell Line
Electrophysiology
Female
Gene Expression Regulation, Developmental
/ genetics
Genetic Predisposition to Disease
/ genetics
Humans
In Situ Hybridization
Induced Pluripotent Stem Cells
/ cytology
Microscopy, Electron
Multigene Family
Naphthoquinones
Organoids
/ cytology
Retina
/ cytology
Single-Cell Analysis
/ methods
Synapses
/ physiology
Transcriptome
/ genetics
eye disease
human retina
macular degeneration
organoid
organoid development
retina
retinal organoid
single cell sequencing
synaptic function
transcriptome
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
17 09 2020
17 09 2020
Historique:
received:
25
07
2019
revised:
14
06
2020
accepted:
06
08
2020
entrez:
18
9
2020
pubmed:
19
9
2020
medline:
20
5
2021
Statut:
ppublish
Résumé
Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers and functional synapses. We sequenced the RNA of 285,441 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas, and performed histochemistry. Cell types in organoids matured in vitro to a stable "developed" state at a rate similar to human retina development in vivo. Transcriptomes of organoid cell types converged toward the transcriptomes of adult peripheral retinal cell types. Expression of disease-associated genes was cell-type-specific in adult retina, and cell-type specificity was retained in organoids. We implicate unexpected cell types in diseases such as macular degeneration. This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in human retinas.
Identifiants
pubmed: 32946783
pii: S0092-8674(20)31004-7
doi: 10.1016/j.cell.2020.08.013
pmc: PMC7505495
pii:
doi:
Substances chimiques
Naphthoquinones
0
histochrome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1623-1640.e34Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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