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Zekai Cui, Jiansu Chen, Yonglong Guo, Xin Yan, Shengru Mao, Yalan Zhou, Shibo Tang; Transcriptomic analysis of retinal organoid development and molecular dynamics. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3324.
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© ARVO (1962-2015); The Authors (2016-present)
The retinal organoids provide a research tool to well understand the molecular dynamics of human retinal development, especially photoreceptors. But the differences in transcriptomics between retinal organoids and native retinal development are still unknown. Here, we used bioinformatics analysis to find the development rule in molecular dynamics of retina between mouse and human.
We used the datasets of mouse retinal development (GSE101986), mouse retinal organoid development (GSE102794), human retinal development (GSE104827) and human retinal organoid development (GSE119320) from the Gene Expression Omnibus. After normalization, differentially expressed genes at each time point in mouse datasets were screened. Genes in human datasets were clustered to classify them over time. Then, gene ontology (GO) terms were used to analyze the biological processes of selected genes and cellular components of photoreceptor cells.
We discover that there are temporal correspondence and consistency between native retinal development and retinal organoid development in mouse and human. The developmental time intervals of various retinal cells are plotted based on above finding (Fig. 1). In early stage, cell proliferation predominates. Then neural differentiation accounts for the majority. While photoreceptor cell differentiation is dominant in later stage. Interestingly, there is a development rule in photoreceptor subcellular components. We find that periciliary membrane compartment and connecting cilium first appear. Then photoreceptor ribbon synapses form. Inner and outer segments develop finally. There are two peaks in mitochondrion-related genes, one in early development and the other in photoreceptor development period (Fig. 2). Additionally, in the comparison of mouse and human retinal organoid development, we find the fatty acid metabolic process and some peroxidases are up-regulated over time, while the glycogen catabolic process and activin receptors are down-regulated over time in human retinal organoid. But these trends are completely opposite in mouse retinal organoid development.
This study has the potential to close the gap between our knowledge in the genetics and biology of retinal development and diseases, which facilitate retinal therapeutic means.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Fig. 1 Timeline of various retinal cells development.
Fig. 2 The expression period of various photoreceptor subcellular components.
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