ArticleInvestigative ophthalmology & visual science2022
Timed Notch Inhibition Drives Photoreceptor Fate Specification in Human Retinal Organoids.
Article in Investigative ophthalmology & visual science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Retinal Organoids from Induced Pluripotent Stem Cells of Patients with Inherited Retinal Diseases: A Systematic Review.Stem cell reviews and reports · 2025Pooled it
- Cell differentiation-related signaling pathways: biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Next-Generation Strategies for Neural Repair and Regeneration: Neural Organoid Transplantation in the CNS.Cell proliferation · 2026Review
- Retinal organoids: current status of development and new avenues for application in disease modeling, drug discovery and therapeutics.International journal of retina and vitreous · 2026Review
- Reporter-guided photoreceptor differentiation in 2D culture using PGP1-hIPSCs: A comparable alternative to 3D organoid systems?Molecular vision · 2026Article
- Bioelectronic Interfaces and Sensors for Neural Organoids.Microsystems & nanoengineering · 2025Review
- Review
- Stimulating the regenerative capacity of the human retina with proneural transcription factors in 3D cultures.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- "ArmedFrontiers in cell and developmental biology · 2025Review
- Robust reprogramming of glia into neurons by inhibition of Notch signaling and nuclear factor I (NFI) factors in adult mammalian retina.Science advances · 2024Article
- Human iPSC-derived photoreceptor transplantation in the cone dominant 13-lined ground squirrel.Stem cell reports · 2024Article
- ASCL1 induces neurogenesis in human Müller glia.Stem cell reports · 2023Article
- A framework to identify functional interactors that contribute to disrupted early retinal development in Vsx2 ocular retardation J mice.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Integrated Transcriptome Analysis of Long Noncoding RNA and mRNA in Developing and Aging Mouse Retina.Scientific data · 2023Article
- Advancements in pre-clinical development of gene editing-based therapies to treat inherited retinal diseases.Vision research · 2023Article
- Reliability of human retina organoid generation from hiPSC-derived neuroepithelial cysts.Frontiers in cellular neuroscience · 2023Article
- A treatment within sight: challenges in the development of stem cell-derived photoreceptor therapies for retinal degenerative diseases.Frontiers in transplantation · 2023Review
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Purpose: Transplanting photoreceptors from human pluripotent stem cell-derived retinal organoids have the potential to reverse vision loss in affected individuals. However, transplantable photoreceptors are only a subset of all cells in the organoids. Hence, the goal of our current study was to accelerate and synchronize photoreceptor differentiation in retinal organoids by inhibiting the Notch signaling pathway at different developmental time-points using a small molecule, PF-03084014 (PF). Methods: Human induced pluripotent stem cell- and human embryonic stem cells-derived retinal organoids were treated with 10 µM PF for 3 days starting at day 45 (D45), D60, D90, and D120 of differentiation. Organoids were collected at post-treatment days 14, 28, and 42 and analyzed for progenitor and photoreceptor markers and Notch pathway inhibition by immunohistochemistry (IHC), quantitative PCR, and bulk RNA sequencing (n = 3-5 organoids from three independent experiments). Results: Retinal organoids collected after treatment showed a decrease in progenitor markers (KI67, VSX2, PAX6, and LHX2) and an increase in differentiated pan-photoreceptor markers (OTX2, CRX, and RCVRN) at all organoid stages except D120. PF-treated organoids at D45 and D60 exhibited an increase in cone photoreceptor markers (RXRG and ARR3). PF treatment at D90 revealed an increase in cone and rod photoreceptors markers (ARR3, NRL, and NR2E3). Bulk RNA sequencing analysis mirrored the immunohistochemistry data and quantitative PCR confirmed Notch effector inhibition. Conclusions: Timing the Notch pathway inhibition in human retinal organoids to align with progenitor competency stages can yield an enriched population of early cone or rod photoreceptors.
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Registered trials
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.