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Retinoblastoma from Human Stem Cell-Derived Retinal Organoids (BeadChIP)

ABSTRACT: Retinoblastoma from Human Stem Cell-Derived Retinal Organoids (BeadChIP)

PROVIDER: PRJNA728727 | ENA |

REPOSITORIES: ENA

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Retinoblastoma from Human Stem Cell-Derived Retinal Organoids (BeadChIP)

Project description:Retinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation of the RB1 gene. To develop a laboratory model of human retinoblastoma formation, we made induced pluripotent stem cells (iPSCs) from 15 participants with germline RB1 mutations. After 45 days in culture, the retinal organoids were dissociated and injected into the vitreous of eyes of immunocompromised mice to support retinoblastoma tumor growth. Retinoblastomas formed from retinal organoids made from patient-derived iPSCs had molecular, cellular and genomic features indistinguishable from human retinoblastomas.

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Project description:Retinoblastoma from Human Stem Cell-Derived Retinal Organoids

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mRNA-seq of retinoblastoma samples

Project description:RNA-seq analysis of five retinoblastoma tumor samples to compare expression signature with retinal organoids generated from hESCs in vitro and modelling retinoblastoma

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Retinoblastoma from human stem cell-derived retinal organoids.

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RB1 depleted pluripotent stem cell retinal organoids recapitulate state cell transitions of retinoblastoma development

Project description:Retinoblastoma (Rb) is a childhood cancer of the developing retina that begins in utero in response to bi-allelic inactivation of RB1 or MYCN amplification, accounting for up to 1% of all tumours in infancy. To gain insights into the transcriptional events of each state cell transition during Rb development, we developed two Rb models via retinal organoid differentiation of RB1 depleted human embryonic stem cell line (RB1-null hESCs) and RB1patient-specific induced pluripotent (iPSC) line harbouring RB1 biallelic mutation (c.2082delC). Both models were characterised by RB1 depletion and a significant increase in the fraction of proliferating cone precursors (RXRγ+Ki67+), which were defined as cell of origin for Rb by the single cell RNA-Seq analysis. The RB1 depleted retinal organoids displayed similar features to Rb tumours including mitochondrial cristae aberration and rosette-like structures and were able to undergo cell growth in an anchorage-independent manner, indicative of cell transformation in vitro. The patient-specific iPSC model displayed an enhanced reduction of amacrine, horizontal and retinal ganglion cells and an accelerated loss of cone photoreceptor markers during transition towards retinoma and Rb, compared to RB1-null hESC. In both models, the Rb cells of origin, intermediate retinoma and/or Rb cells expressed retinal ganglion and horizontal cell in addition to cone markers, a novel finding, which should help to better identify and eradicate these cells within the tumour mass. Application of Melphalan, Topotecan and TW-37 led to a significant reduction in the fraction of proliferating cone precursors, validating the suitability of these in vitro models for testing novel therapeutics for Rb.

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Modeling human retinoblastoma using embryonic stem cell-derived retinal organoids.

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Molecular pathology of Usher 1B patient-derived retinal organoids at single cell resolution

Project description:Compare single cell transcriptomes of control and USH1B patient iPSC-derived retinal organoids to elucidate disease mechanisms of Usher syndrome type IB (USH1B). USH1B patient fibroblasts were collected at Great Ormond Street Hospital (GOSH) and reprogrammed to iPSCs. Control and patient iPSCs differentiated in vitro to generate retinal organoids and collected at 35wks. Sequencing was performed at GENEWIZ (Azenta life sciences) on a Illumina NovaSeq system. Data aligned to the human genome UCSC hg38 using cellranger package.

2023-03-27 | E-MTAB-11990 | biostudies-arrayexpress

Single-Cell RNA Sequencing of Retinal Organoids Derived by CSC14 hESCs

Project description:Retinal organoids samples that derived from human embryonic stem cells were analyzed by single-cell RNA sequencing. Two samples at different differentiation stages (day57 and day 171) were included in this study for cell type comparison.

2022-01-01 | E-MTAB-11121 | biostudies-arrayexpress

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