Evidence map›Paper›PMID 31814692›Full record

ArticleMolecular vision2019

Transcriptome-based molecular staging of human stem cell-derived retinal organoids uncovers accelerated photoreceptor differentiation by 9-cis retinal.

Koray D Kaya, Holly Y Chen, Matthew J Brooks, Ryan A Kelley, Hiroko Shimada, Kunio Nagashima, Natalia de Val, Charles T Drinnan, Linn Gieser, Kamil Kruczek and 6 more

Abstract read
PubMed Full text at PMC
In one paragraph

Article in Molecular vision, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 1 synthesis or guideline pooled it.

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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Koray D KayaNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Holly Y ChenNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Matthew J BrooksNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Ryan A KelleyNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Hiroko ShimadaNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Kunio NagashimaElectron Microscopy Laboratory, National Cancer Institute, Center for Cancer Research, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD.
Natalia de ValElectron Microscopy Laboratory, National Cancer Institute, Center for Cancer Research, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD.
Charles T DrinnanNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Linn GieserNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Kamil KruczekNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Slaven ErcegStem Cell Therapies for Neurodegenerative Diseases Lab and National Stem Cell Bank - Valencia Node, Research Center Principe Felipe, Valencia, Spain.
Tiansen LiNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Dunja LukovicRetinal Degeneration Lab and National Stem Cell Bank - Valencia Node, Research Center Principe Felipe, Valencia, Spain.
Yogita K AdlakhaNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Emily WelbyNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.
Anand SwaroopNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD.

Funding

Regulation of retinal developmentZIAEY000450 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2009 to 2025
$71.0M
Biological function microRNAs enriched in RPE: in vitro and in vivo modelsZIAEY000456 · NEI · NATIONAL EYE INSTITUTE · PI SCHNEEWEIS, DAVID · 2009 to 2020
$9.5M
CCR NIH HHS HHSN261200800001CIntramural NIH HHS ZIA EY000450Intramural NIH HHS ZIA EY000456NCI NIH HHS HHSN261200800001ENEI NIH HHS ZIA EY000450NEI NIH HHS ZIA EY000456
6 · The paper itself

Abstract

purposeRetinal 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.

methodsWe 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.

resultsWe 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.

conclusionOur 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.

Indexed as

Cell DifferentiationCell LineCell ShapeDiterpenesGene Expression ProfilingHuman Embryonic Stem CellsHumansInduced Pluripotent Stem CellsOrganoidsRetinaRetinaldehydeRetinal Rod Photoreceptor CellsTranscriptome9-cis-retinalDiterpenesRetinaldehyde

Identifiers

PMID31814692
PMCPMC6857775

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.