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A comprehensive characterisation of fetal and mature retinal cell identity to assess the fidelity of retinal organoids

ABSTRACT: Retinal organoids derived from pluripotent stem cells have been widely used to model development and disease of the human eye. Yet there is a lack of studies that have systematically evaluated the fidelity of the organoids to their in vivo counterpart. This is particularly relevant for evaluating the efficacy of therapeutic applications and culture protocol performance. To this end, we performed an extensive meta-atlas characterisation of cellular identities of the human eye, covering a wide range of developmental stages. The resulting map uncovered previously unknown biomarkers of major retinal cell types and those associated with cell-type specific maturation. Using these retinal identities from fetal and adult tissue as the map, we systematically assessed the fidelity of the retinal organoids to mimic the human eye, enabling us to comprehensively benchmark the current protocols for retinal organoid generation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE201356 | GEO | 2022/12/10

REPOSITORIES: GEO

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A comprehensive characterisation of fetal and mature retinal cell identity to assess the fidelity of retinal organoids

Project description:A comprehensive characterisation of fetal and mature retinal cell identity to assess the fidelity of retinal organoids

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Stage-specific dynamic reorganization of genome topology shapes transcriptional neighborhoods in developing human retinal organoids

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Stage-specific dynamic reorganization of genome topology shapes transcriptional neighborhoods in developing human retinal organoids

Project description:This SuperSeries is composed of the SubSeries listed below. We have generated high-resolution Hi-C map of developing human retinal organoids to elucidate spatiotemporal dynamics of genomic architecture and its relationship with gene expression patterns. We demonstrate progressive and developmental stage-specific alterations in DNA topology and correlate these changes with transcription of cell type-restricted gene markers during retinal differentiation. Temporal Hi-C reveals a shift towards A compartment for protein-coding genes and B compartment for non-coding RNAs, displaying high and low expression respectively. Notably, retina-enriched genes are clustered near lost boundaries of topologically associated domains (TADs), and higher-order assemblages of TADs (i.e., TAD cliques) tend to localize in the active chromatin regions with binding sites for eye-field transcription factors. These genes show a gain of chromatin contacts at their transcription start site as organoid differentiation proceeds. Our study provides a global view of chromatin architecture dynamics associated with diversification of cell types during retinal development and serves as a foundational resource for in-depth functional investigations of retinal developmental traits.

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Transcriptomic features of hiPSC-derived cells with a good capability to generate retinal organoids

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Transcription profiling of human and mouse first passage vs. primary retinal sphere cells

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Single cell transcriptomic comparison of human fetal retina, hPSC-derived retinal organoids, and long-term retinal cultures.

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2023-02-24 | E-MTAB-12622 | biostudies-arrayexpress

Deciphering the spatio-temporal transcriptional and chromatin accessibility of human retinal organoid development at the single cell level [Spatial Transcriptomics]

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