Retinoblastoma from Human Stem Cell-Derived Retinal Organoids (BeadChIP)
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ABSTRACT:
PROVIDER: PRJNA728727 | ENA |
REPOSITORIES: ENA
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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.
2021-05-11 | GSE174201 | GEO
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.
2021-05-11 | GSE174200 | GEO
Project description:Retinoblastoma from Human Stem Cell-Derived Retinal Organoids
| PRJNA728725 | ENA
Project description:Retinoblastoma from Human Stem Cell-Derived Retinal Organoids (RNA-Seq)
| PRJNA728722 | ENA
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
2022-05-10 | E-MTAB-10330 | biostudies-arrayexpress
Project description:Recent in vitro studies using RB1+/- fibroblasts and MSCs have shown molecular and functional disruptions without the need for biallelic loss of RB1. However, this was not reflected in the recent in vitro studies employing RB1+/- retinal organoids. To gain further insights into the molecular disruptions in the RB1+/- retinal organoids we performed a high throughput RNA-sequencing analysis.iPSCs were generated from RB1+/+ and RB1+/- Orbital adipose mesenchymal stem cells (OAMSCs) derived from retinoblastoma patients. RB1+/+ and RB1+/- iPSCs were subjected to step-wise retinal differentiation protocol and high throughput RNA-sequencing followed by differential gene expression analysis and Gene set enrichment analysis (GSEA) was performed.The analysis revealed that even though there are no gross observable differences, subtle molecular changes in RB1+/- retinal organoids were observed. We report that there is mild shift from the regular metabolic process of glycolysis to oxidative phosphorylation in the RB1+/- retinal organoids which could be setting a premise for tumorigenesis.
2024-05-29 | GSE255268 | GEO
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
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
Project description:Retinitis pigmentosa (RP) is an irreversible and inherited retinopathy. RPGR mutations are the most common causes of this disease. It remains challenging to decipher the mechanism of RPGR mutation because of the lack of appropriate study models. The substitution of patient-specific diseased retina without ethical restrictions is desired and iPSC-derived 3D retina is the best choice. In our experiment, we generated iPSCs from one RP patient with 2-bp frameshift mutation in the exon14 of RPGR gene, which were differentiated into retinal organoids. Also we generated iPSCs from a normal control and differentiated those control-iPSCs into healthy retinal organoids. Samples of patient- and control-retinal organoids at W0, W7, W13 (two replicates), W18 (two replicates) and W22 (two replicates for patient) were collected for RNA-seq. Corrected-iPSC were derived from CRISPR/Cas9-mediated gene correction. Then we collected the corrected-iPSC derived retinal organoids at W0, W7, W13 (two replicates), W18 (two replicates) and W22 (two replicates) for RNA-seq. Through the RNA-seq data, we demonstrate that patient-specific iPSC-dervied 3D retinae can recapitulate disease progress of Retinitis Pigmentosa through presenting defects in photoreceptors' gene profile. CRISPR/Cas9-mediated gene correction can rescue photoreceptor gene profile. Those transcriptome are consistent with the phenotype and function.
2020-02-01 | E-MTAB-6490 | biostudies-arrayexpress
Project description:Microglia are the primary resident immune cells in the retina. They regulate neuronal survival and synaptic pruning, which makes them essential for normal development. Following injury, they mediate adaptive responses and under pathological conditions can trigger neurodegeneration exacerbating the effect of the disease. Retinal organoids derived from human induced pluripotent stem cells (hiPSCs) are increasingly used for a range of applications, including disease modelling, development of new therapies and in the study of retinogenesis. Despite their close resemblance to the in vivo retina, they lack some key physiological features including immune cells. To enhance the retinal organoid model, we engineered an hiPSC co-culture system containing the hiPSC-derived retinal organoids and hiPSC-derived microglia-like (iMG) cells and tested their retinal invasion capacity and function. We incorporated iMG into retinal organoids at 13 weeks and tested their effect on function and development at 15 and 21.5 weeks of differentiation. Our key findings showed that iMG cells were able to respond to endotoxin challenge in monocultures and when co-cultured with the organoids. Single cell RNA-Seq transcriptomic analyses, protein expression, electron microscopy imaging and electrophysiological recordings showed that retinal organoids developed normally, expressed key markers, and retained their ability to generate spiking activity in response to light. Thus, this new co-culture immunocompetent in vitro retinal model provides a platform with greater relevance to the in vivo human retina.
2023-05-17 | GSE173180 | GEO