Evidence map›Paper›PMID 26235913›Full record

ArticleStem cells (Dayton, Ohio)2015

Transcriptome Dynamics of Developing Photoreceptors in Three-Dimensional Retina Cultures Recapitulates Temporal Sequence of Human Cone and Rod Differentiation Revealing Cell Surface Markers and Gene Networks.

Rossukon Kaewkhaw, Koray Dogan Kaya, Matthew Brooks, Kohei Homma, Jizhong Zou, Vijender Chaitankar, Mahendra Rao, Anand Swaroop

Open access · hybridAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed
8.3field-weighted citation impact, top 2% of its field
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

104 citing papers in PubMed, 164 citations in OpenAlex.

  1. Article
  2. A cell fate specification and transition mechanism for human foveolar cone subtype patterning.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  8. Review
  9. Retinal Neurochemistry.Brain sciences · 2025
    Review
  10. Rekindling Vision: Innovative Strategies for Treating Retinal Degeneration.International journal of molecular sciences · 2025
    Review
  11. Article
  12. Review
  13. Article
  14. Progenitor division and cell autonomous neurosecretion are required for rod photoreceptor sublaminar positioning.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Sunitinib efficacy with minimal toxicity in patient-derived retinoblastoma organoids.Journal of experimental & clinical cancer research : CR · 2023
    Article
  20. Review

44 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

8 authors at 5 institutions in 3 countries.

Rossukon KaewkhawNeurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Koray Dogan KayaNeurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Matthew BrooksNeurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Kohei HommaNeurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Jizhong ZouCenter for Regenerative Medicine, National Institutes of Health, Bethesda, Maryland, USA.
Vijender ChaitankarNeurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Mahendra RaoCenter for Regenerative Medicine, National Institutes of Health, Bethesda, Maryland, USA.
Anand SwaroopNeurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
National Institutes of Health · USCenter for Neuroscience and Regenerative Medicine · USNational Eye Institute · USNew York Stem Cell Foundation · USRamathibodi Hospital · TH

Funding

Regulation of retinal developmentZIAEY000450 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2009 to 2025
$71.0M
NHLBI iPSC Core FacilityZICHL006145 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI ZOU, JIZHONG · 2012 to 2025
$23.3M
Interventional approaches for restoring visionZIAEY000474 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2009 to 2019
$15.5M
Regulation of gene expression in the retinaZ01EY000450 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2008 to 2008
$2.4M
Intramural NIH HHS Z01 EY000450Intramural NIH HHS ZIA EY000450Intramural NIH HHS ZIA EY000474NEI NIH HHS EY000474
6 · The paper itself

Abstract

The derivation of three-dimensional (3D) stratified neural retina from pluripotent stem cells has permitted investigations of human photoreceptors. We have generated a H9 human embryonic stem cell subclone that carries a green fluorescent protein (GFP) reporter under the control of the promoter of cone-rod homeobox (CRX), an established marker of postmitotic photoreceptor precursors. The CRXp-GFP reporter replicates endogenous CRX expression in vitro when the H9 subclone is induced to form self-organizing 3D retina-like tissue. At day 37, CRX+ photoreceptors appear in the basal or middle part of neural retina and migrate to apical side by day 67. Temporal and spatial patterns of retinal cell type markers recapitulate the predicted sequence of development. Cone gene expression is concomitant with CRX, whereas rod differentiation factor neural retina leucine zipper protein (NRL) is first observed at day 67. At day 90, robust expression of NRL and its target nuclear receptor NR2E3 is evident in many CRX+ cells, while minimal S-opsin and no rhodopsin or L/M-opsin is present. The transcriptome profile, by RNA-seq, of developing human photoreceptors is remarkably concordant with mRNA and immunohistochemistry data available for human fetal retina although many targets of CRX, including phototransduction genes, exhibit a significant delay in expression. We report on temporal changes in gene signatures, including expression of cell surface markers and transcription factors; these expression changes should assist in isolation of photoreceptors at distinct stages of differentiation and in delineating coexpression networks. Our studies establish the first global expression database of developing human photoreceptors, providing a reference map for functional studies in retinal cultures.

Indexed as

Cell DifferentiationTranscriptomeAntigens, DifferentiationCell LineEye ProteinsHuman Embryonic Stem CellsHumansRetinal Cone Photoreceptor CellsRetinal Rod Photoreceptor CellsAntigens, DifferentiationEye ProteinsGlobal gene profilingHuman rod and cone photoreceptorsNext generation sequencingRetinaStem cellsThree-dimensional organoid culture

Identifiers

PMID26235913
PMCPMC4713319
OpenAlexW1843828601

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

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.