Evidence map›Paper›PMID 42031716›Full record

ArticleNature communications2026

Retinoic acid drives cell fate specification, maturation and retinal regionality in human retinal organoids.

Benjamin Y Lim, Carissa Chen, Anna Fredericks, Elham Nilli, Santiago Mesa Mora, Megan Weatherstone, To Ha Loi, Peter Newman, Nader Aryamanesh, Hala Zreiqat and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Article
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

13 authors.

Benjamin Y Lim *Stem Cell Medicine Unit, Children's Medical Research Institute, Westmead, NSW, Australia.
Carissa Chen *School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia.ORCID http://orcid.org/0000-0002-9225-7086
Anna FredericksSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia.ORCID http://orcid.org/0009-0008-9559-5831
Elham NilliStem Cell Medicine Unit, Children's Medical Research Institute, Westmead, NSW, Australia.
Santiago Mesa MoraStem Cell Medicine Unit, Children's Medical Research Institute, Westmead, NSW, Australia.
Megan WeatherstoneSingle Cell Analytics Facility, Children's Medical Research Institute, Westmead, NSW, Australia.
To Ha LoiEye Genetics Research Unit, Children's Medical Research Institute, Westmead, NSW, Australia.
Peter NewmanSchool of Biomedical Engineering, Faculty of Engineering, University of Sydney, Camperdown, NSW, Australia.ORCID http://orcid.org/0000-0002-5202-4819
Nader AryamaneshBioinformatics Facility, Children's Medical Research Institute, Westmead, NSW, Australia.ORCID http://orcid.org/0000-0003-4666-9175
Hala ZreiqatSchool of Biomedical Engineering, Faculty of Engineering, University of Sydney, Camperdown, NSW, Australia.ORCID http://orcid.org/0000-0003-0521-7711
Patrick TamSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia.ORCID http://orcid.org/0000-0001-6950-8388
Pengyi YangComputational Systems Biology Unit, Children's Medical Research Institute, Westmead, NSW, Australia. pengyi.yang@sydney.edu.au.ORCID http://orcid.org/0000-0003-1098-3138
Anai Gonzalez-CorderoStem Cell Medicine Unit, Children's Medical Research Institute, Westmead, NSW, Australia. agonzalez-cordero@cmri.org.au.ORCID http://orcid.org/0000-0002-1818-0375

Funding

Department of Health | National Health and Medical Research Council (NHMRC) 1173469
6 · The paper itself

Abstract

Retinoic acid (RA) is a key morphogen in human retinal development, activating transcriptional programs that drive retinal progenitor differentiation and photoreceptor development, ensuring proper spatial organisation within the neural retina, essential for vision. Despite its well-established role in retinal patterning, the concentration-dependent effects of RA on human retinal cell fate specification and the regional definition of the primate macula and peripheral retina remain poorly understood. Here, we show that temporal and dosage-dependant modulation of RA during human retinal organoid differentiation induces distinct changes in retinal cell abundance, maturation, and organisation. Single-cell transcriptomics and protein analysis reveal that RA dosage influences the relative abundance and maturation of photoreceptors and retinal interneurons. Spatial transcriptomics analyses demonstrates that low RA levels biases retinal organoids toward a macular-like regional identity, whereas high RA levels promotes peripheral-like development. Collectively, our findings emphasise the critical role of RA signalling in retinal maturation and regional specification. This study elucidates mechanisms involved in human retinal development and we anticipate that controlled RA modulation in retinal organoids provides a strategy to refine disease modelling of inherited retinal disorders and enhance the specific generation of photoreceptors suitable for transplantation and regenerative therapies.

Indexed as

Cell DifferentiationOrganoidsRetinaTretinoinGene Expression Regulation, DevelopmentalHumansSignal TransductionTretinoin

Identifiers

PMID42031716
PMCPMC13319458

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.