Evidence map›Paper›PMID 41394566›Full record

ArticlebioRxiv : the preprint server for biology2025

Dynamic changes in mRNA isoform usage during human retinal development.

Casey J Keuthan, Sowmya Parthiban, Yen-Yu Chang, Xiaoqian Shan, Xiaoli Chang, Ethan Yan, Sheridan Cavalier, Winston Timp, Stephanie C Hicks, Donald J Zack

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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. 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

10 authors.

Casey J KeuthanDepartment of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0001-9422-490X
Sowmya ParthibanDepartment of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Yen-Yu ChangDepartment of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Xiaoqian ShanDepartment of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Xiaoli ChangDepartment of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Ethan YanDepartment of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Sheridan CavalierDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-3494-1450
Winston TimpDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-2083-6027
Stephanie C HicksDepartment of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-7858-0231
Donald J ZackDepartment of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0002-7966-1973

Funding

Computational Methods for Emerging Spatially-resolved Transcriptomics with Multiple SamplesR35GM150671 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Stephanie Carinne Hicks · 2023 to 2026
$1.2M
Investigating the Alternative Splicing Landscape of Human Retinal Development and DegenerationK99EY035737 · NEI · JOHNS HOPKINS UNIVERSITY · PI KEUTHAN, CASEY · 2024 to 2025
$221k
NEI NIH HHS K99 EY035737NIGMS NIH HHS R35 GM150671
6 · The paper itself

Abstract

Background: Alternative mRNA splicing is a key mechanism for generating isoform diversity in eukaryotic cells. However, the extent of the splicing changes that occur during complex regulatory processes like neurodevelopment are still incompletely characterized. Results: We performed nanopore-based long-read RNA sequencing on differentiating human stem cell-derived retinal organoids to identify temporal patterns of isoform usage across developmental stages. We found that retinal organoids undergo dynamic shifts in isoform usage throughout differentiation, which were not necessarily accompanied with changes in overall gene expression, as was the case for many genes involved in the regulation of mRNA splicing itself. Further analysis of human stem cell-derived retinal ganglion cells uncovered neuron-specific splicing signatures. Additionally, allele-specific expression analysis revealed extensive allelic imbalance in induced pluripotent stem cell-derived organoid cultures. Conclusions: By combining direct long-read RNA sequencing with human stem cell retinal models we could explore isoform-level changes in differentiating human cells at unprecedented detail. These results uncovered dynamic shifts in transcript usage during retinal differentiation, adding to our knowledge base of post-transcriptional RNA processing in the developing central nervous system and human

Indexed as

isoformslong-read sequencingnanoporeneurodevelopmentorganoidsretinaRNAsplicingstem cellstranscriptomics

Identifiers

PMID41394566
PMCPMC12697546

What OpenQuestion holds

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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.