ArticleStem cells translational medicine2022
pRB-Depleted Pluripotent Stem Cell Retinal Organoids Recapitulate Cell State Transitions of Retinoblastoma Development and Suggest an Important Role for pRB in Retinal Cell Differentiation.
Article in Stem cells translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Retinal Organoids from Induced Pluripotent Stem Cells of Patients with Inherited Retinal Diseases: A Systematic Review.Stem cell reviews and reports · 2025Pooled it
- Retinal organoid screening reveals ABT-737 and luminespib as potential agents against a cone- precursor-derived subtype of retinoblastoma.Molecular therapy. Oncology · 2026Article
- Retinoblastoma: unveiling molecular pathogenesis and pioneering organoid-driven therapeutic innovations.Stem cell research & therapy · 2026Review
- Longitudinal analysis of retinal cell state transitions in RB1-deficient retinal organoids reveals the nascent cone precursors are the earliest cell-origin of human retinoblastoma.Cell death & disease · 2026Article
- Genetic and chromosomal dysregulations of progenitor cells in the etiology and pathogenesis of pediatric cancers.American journal of stem cells · 2026Review
- Organoid models: reshaping the paradigm for precision development and evaluation of CAR-T cell therapies.Frontiers in bioengineering and biotechnology · 2026Review
- Molecular crosstalk between MASLD and IVDD revealed through integrated biomarker discovery analysis.Frontiers in immunology · 2026Article
- Progress of iPSC-derived retinal organoids in the study of inherited retinal diseases.Orphanet journal of rare diseases · 2025Review
- Genetics and current research models of Mendelian tumor predisposition syndromes with ocular involvement.Progress in retinal and eye research · 2025Review
- Retinal Organoids: Innovative Tools for Understanding Retinal Degeneration.International journal of molecular sciences · 2025Review
- Decoding cancer etiology with cellular reprogramming.Current opinion in genetics & development · 2025Review
- Optimized Prime Editing of Human Induced Pluripotent Stem Cells to Efficiently Generate Isogenic Models of Mendelian Diseases.International journal of molecular sciences · 2024Article
- Heterozygous RB1 mutation enhanced ATP production in human iPSC-derived retinal organoids.Molecular biology reports · 2024Article
- Single-cell analyses reveal transient retinal progenitor cells in the ciliary margin of developing human retina.Nature communications · 2024Article
- Application Prospect of Induced Pluripotent Stem Cells in Organoids and Cell Therapy.International journal of molecular sciences · 2024Review
- Classical and Innovative Evidence for Therapeutic Strategies in Retinal Dysfunctions.International journal of molecular sciences · 2024Review
- Inhibition of high level E2F in a RB1 proficient MYCN overexpressing chicken retinoblastoma model normalizes neoplastic behaviour.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Advanced Cellular Models for Rare Disease Study: Exploring Neural, Muscle and Skeletal Organoids.International journal of molecular sciences · 2024Review
- Retinal organoids provide unique insights into molecular signatures of inherited retinal disease throughout retinogenesis.Journal of anatomy · 2023Review
- Sunitinib efficacy with minimal toxicity in patient-derived retinoblastoma organoids.Journal of experimental & clinical cancer research : CR · 2023Article
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Abstract
Retinoblastoma (Rb) is a childhood cancer of the developing retina, accounting for up to 17% of all tumors in infancy. To gain insights into the transcriptional events of cell state transitions during Rb development, we established 2 disease models via retinal organoid differentiation of a pRB (retinoblastoma protein)-depleted human embryonic stem cell line (RB1-null hESCs) and a pRB patient-specific induced pluripotent (iPSC) line harboring a RB1 biallelic mutation (c.2082delC). Both models were characterized by pRB depletion and accumulation of retinal progenitor cells at the expense of amacrine, horizontal and retinal ganglion cells, which suggests an important role for pRB in differentiation of these cell lineages. Importantly, a significant increase in the fraction of proliferating cone precursors (RXRγ+Ki67+) was observed in both pRB-depleted organoid models, which were defined as Rb-like clusters by single-cell RNA-Seq analysis. The pRB-depleted retinal organoids displayed similar features to Rb tumors, including mitochondrial cristae aberrations and rosette-like structures, and were able to undergo cell growth in an anchorage-independent manner, indicative of cell transformation in vitro. In both models, the Rb cones expressed retinal ganglion and horizontal cell markers, a novel finding, which could help to better characterize these tumors with possible therapeutic implications. Application of Melphalan, Topotecan, and TW-37 led to a significant reduction in the fraction of Rb proliferating cone precursors, validating the suitability of these in vitro models for testing novel therapeutics for Rb.
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