Transcriptome-based molecular staging of human stem cell-derived retinal organoids uncovers accelerated photoreceptor differentiation by 9-cis retinal.
Cell Differentiation
/ drug effects
Cell Line
Cell Shape
/ drug effects
Diterpenes
/ pharmacology
Gene Expression Profiling
Human Embryonic Stem Cells
/ cytology
Humans
Induced Pluripotent Stem Cells
/ cytology
Organoids
/ cytology
Retina
/ cytology
Retinal Rod Photoreceptor Cells
/ cytology
Retinaldehyde
/ pharmacology
Transcriptome
/ drug effects
Journal
Molecular vision
ISSN: 1090-0535
Titre abrégé: Mol Vis
Pays: United States
ID NLM: 9605351
Informations de publication
Date de publication:
2019
2019
Historique:
received:
26
08
2019
accepted:
08
11
2019
entrez:
10
12
2019
pubmed:
10
12
2019
medline:
20
6
2020
Statut:
epublish
Résumé
Retinal organoids generated from human pluripotent stem cells exhibit considerable variability during differentiation. Our goals are to assess developmental maturity of the neural retina in vitro and design improved protocols based on objective criteria. We performed transcriptome analyses of developing retinal organoids from human embryonic and induced pluripotent stem cell lines and utilized multiple bioinformatic tools for comparative analysis. Immunohistochemistry, immunoblotting and electron microscopy were employed for validation. We show that the developmental variability in organoids was reflected in gene expression profiles and could be evaluated by molecular staging with the human fetal and adult retinal transcriptome data. We also demonstrate that the addition of 9-cis retinal, instead of the widely used all-trans retinoic acid, accelerated rod photoreceptor differentiation in organoid cultures, with higher rhodopsin expression and more mature mitochondrial morphology evident by day 120. Our studies provide an objective transcriptome-based modality for determining the differentiation state of retinal organoids and for comparisons across different stem cell lines and platforms, which should facilitate disease modeling and evaluation of therapies in vitro.
Substances chimiques
Diterpenes
0
9-cis-retinal
514-85-2
Retinaldehyde
RR725D715M
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
663-678Subventions
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NEI NIH HHS
ID : ZIA EY000456
Pays : United States
Organisme : NEI NIH HHS
ID : ZIA EY000450
Pays : United States
Informations de copyright
Copyright © 2019 Molecular Vision.
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