Evidence map›Paper›PMID 41791386›Full record

ArticleStem cell reports2026

Genomic characterization of sub-populations in human pluripotent stem cell-derived retinal progenitor cells driving retinal lamination.

Yasuaki Iwama, Tomohiro Masuda, Mika Yoshimura, Mikiya Watanabe, Yoko Ohigashi, Martin Friedlander, Kohji Nishida, Masayo Takahashi, Itoshi Nikaido, Michiko Mandai

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 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

10 authors.

Yasuaki IwamaLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan; Research Center, Kobe City Eye Hospital, Kobe, Hyogo 650-0047, Japan; Department of Ophthalmology Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan; Department of Molecular and Cellular Biology, Scripps Research, La Jolla, CA 92037, USA. Electronic address: yasuaki_iwama@kcho.jp.
Tomohiro MasudaLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan; Research Center, Kobe City Eye Hospital, Kobe, Hyogo 650-0047, Japan. Electronic address: tomohiro_masuda@kcho.jp.
Mika YoshimuraOmics AI Research Team, Advanced General Intelligence in Science Program (AGIS), TRIP Headquarters, RIKEN, Kobe, Hyogo 650-0047, Japan.
Mikiya WatanabeGraduate School of Pharmacy, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.
Yoko OhigashiLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan.
Martin FriedlanderDepartment of Molecular and Cellular Biology, Scripps Research, La Jolla, CA 92037, USA.
Kohji NishidaDepartment of Ophthalmology Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan; Osaka University Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), Osaka 565-0871, Japan.
Masayo TakahashiLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan; Research Center, Kobe City Eye Hospital, Kobe, Hyogo 650-0047, Japan.
Itoshi NikaidoOmics AI Research Team, Advanced General Intelligence in Science Program (AGIS), TRIP Headquarters, RIKEN, Kobe, Hyogo 650-0047, Japan; Department of Functional Genome Informatics, Division of Biological Data Science, Medical Research Laboratory (MRL), Institute of Integrated Research (IIR), Institute of Science Tokyo, Bunkyo, Tokyo 113-0034, Japan.
Michiko MandaiLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan; Research Center, Kobe City Eye Hospital, Kobe, Hyogo 650-0047, Japan. Electronic address: e_lab.mandai@kcho.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The mechanism underlying retinal spheroid layer formation was investigated using Rax::GFP-positive retinal progenitor cells from human embryonic stem cell-derived retinal organoids. Single-cell RNA sequencing suggested the earlier cell-cycle exit in non-layered spheroids, while well-layered spheroids retained longer proliferative property with transiently activated canonical WNT2B-FZD7 signaling followed by temporary expression of non-canonical WNT5A. Despite structural differences in vitro, however, both non-layered and well-layered retinal spheroids on differentiation day 60 developed a layer of photoreceptors after transplantation in a retinal degeneration rat model, resulting in synaptic and functional integration. Additionally, part of the Rax::GFP-positive cells differentiated into non-retinal lineages, including ciliary marginal zone-like, retinal pigment epithelium, and spinal cord-like tissues in vitro, reflecting the heterogeneity of RAX-positive cells. These findings suggest that canonical and non-canonical WNT signaling pathways sequentially orchestrate early retinal morphogenesis, whereas environmental factors within the host retina strongly drive the alignment and functional integration of graft photoreceptors.

Indexed as

GenomicsPluripotent Stem CellsRetinaAnimalsCell DifferentiationHuman Embryonic Stem CellsHumansOrganoidsRatsRetinal DegenerationRetinal Pigment EpitheliumSpheroids, CellularWnt Signaling Pathwaycanonical WNT signaling pathwaycell-based therapyhuman tissuenon-canonical WNT signaling pathwayregenerative therapyretinal layer structuresretinal organoidretinal progenitor cell

Identifiers

PMID41791386
PMCPMC13083797

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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.