Evidence map›Paper›PMID 38870053›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2024

A highly reproducible and efficient method for retinal organoid differentiation from human pluripotent stem cells.

Jade Harkin, Kiersten H Peña, Cátia Gomes, Melody Hernandez, Sailee S Lavekar, Kaman So, Kelly Lentsch, Elyse M Feder, Sarah Morrow, Kang-Chieh Huang and 4 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing 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

46 citing papers in PubMed.

  1. Article
  2. Review
  3. Glycosylation of the retina.Biochemical Society transactions · 2026
    Review
  4. Article
  5. Review
  6. Review
  7. Neuroinflammation in glaucoma: a myriad of cellular pathways and players.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Organoids for disease modeling and treatment: state-of-the-art.Experimental hematology & oncology · 2026
    Review
  17. Review
  18. AAV-mediated exon skipping therapy for Usher syndrome, type 2A.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  19. Article
  20. Review
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

14 authors.

Jade HarkinDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202.
Kiersten H PeñaStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Cátia GomesStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Melody HernandezStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.ORCID 0000-0003-1338-1490
Sailee S LavekarStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.ORCID 0000-0002-1629-3536
Kaman SoDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202.
Kelly LentschStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Elyse M FederStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Sarah MorrowStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Kang-Chieh HuangStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Kaylee D TutrowStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Ann MorrisDepartment of Biology, University of Kentucky, Lexington, KY 40506.ORCID 0000-0003-1489-4431
Chi ZhangDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202.ORCID 0000-0001-9553-0925
Jason S MeyerDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202.ORCID 0000-0001-9037-6033

Funding

Overcoming Barriers to retinal ganglion cell replacement in experimental glaucomaU24EY033269 · NEI · INDIANA UNIVERSITY INDIANAPOLIS · PI FORTUNE, BRAD, MEYER, JASON STEPHEN · 2021 to 2025
$7.0M
Indiana Medical Scientist/Engineer Training ProgramT32GM148382 · NIGMS · INDIANA UNIVERSITY INDIANAPOLIS · PI Benjamin Gaston, Emily K Sims · 2023 to 2026
$3.9M
Establishing a human cellular model of retinal ganglion cell compartmentalization in neurodegeneration and neuroinflammationR01EY033022 · NEI · INDIANA UNIVERSITY INDIANAPOLIS · PI Jason Stephen Meyer · 2021 to 2026
$2.7M
Functions of chromatin remodeler Chd7 in retinal cell developmentR01EY035110 · NEI · UNIVERSITY OF KENTUCKY · PI Donna M. Martin, Jason Stephen Meyer · 2023 to 2026
$2.5M
Development of data driven and AI empowered systems biology to study human diseasesR35GM150971 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Chi Zhang · 2023 to 2026
$1.6M
BrightFocus Foundation (BFF) G2020369BrightFocus Foundation (BFF) G2022003FHHS | NIH | National Eye Institute (NEI) R01EY033022HHS | NIH | National Eye Institute (NEI) U24EY033269NEI NIH HHS R01 EY033022NEI NIH HHS U24 EY033269NIGMS NIH HHS R35 GM150971
6 · The paper itself

Abstract

Human pluripotent stem cell (hPSC)-derived retinal organoids are three-dimensional cellular aggregates that differentiate and self-organize to closely mimic the spatial and temporal patterning of the developing human retina. Retinal organoid models serve as reliable tools for studying human retinogenesis, yet limitations in the efficiency and reproducibility of current retinal organoid differentiation protocols have reduced the use of these models for more high-throughput applications such as disease modeling and drug screening. To address these shortcomings, the current study aimed to standardize prior differentiation protocols to yield a highly reproducible and efficient method for generating retinal organoids. Results demonstrated that through regulation of organoid size and shape using quick reaggregation methods, retinal organoids were highly reproducible compared to more traditional methods. Additionally, the timed activation of BMP signaling within developing cells generated pure populations of retinal organoids at 100% efficiency from multiple widely used cell lines, with the default forebrain fate resulting from the inhibition of BMP signaling. Furthermore, given the ability to direct retinal or forebrain fates at complete purity, mRNA-seq analyses were then utilized to identify some of the earliest transcriptional changes that occur during the specification of these two lineages from a common progenitor. These improved methods also yielded retinal organoids with expedited differentiation timelines when compared to traditional methods. Taken together, the results of this study demonstrate the development of a highly reproducible and minimally variable method for generating retinal organoids suitable for analyzing the earliest stages of human retinal cell fate specification.

Indexed as

Cell DifferentiationOrganoidsPluripotent Stem CellsRetinaBone Morphogenetic ProteinsHumansReproducibility of ResultsSignal TransductionBone Morphogenetic Proteinsorganoidretinastem cell

Identifiers

PMID38870053
PMCPMC11194494

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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.