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A systems biology approach uncovers novel disease mechanisms in age-related macular degeneration.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE220627 | GEO | 2023/09/15

REPOSITORIES: GEO

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A systems biology approach uncovers novel disease mechanisms in age-related macular degeneration [mouse_retina_scRNAseq]

Project description:We investigated the cell type composition of mouse retinas and identified which cell type(s) express genes we identified as being AMD-associated in human patients. We generated Dram2 KO mice to investigate how DRAM2 loss affects the mouse retina. Our in vitro data showed that DRAM2 loss affects human stem cell-derived eye organoids, we investigate if it is the case in mice.

2023-09-15 | GSE220626 | GEO

A systems biology approach uncovers novel disease mechanisms in age-related macular degeneration [mouse_choroid_scRNAseq]

Project description:We are investigating the AMD-associated gene DRAM2. Our in vitro data showed that DRAM2 loss in human embryonic stem cell derived eye organoids generates a distinct fibroblast-like population secreting proteins related to connective tissue extracellular matrix. We generated Dram2 KO mice and did scRNA-seq on cells from the retina, and did not find any significant difference between DRAM2 KO and WT. However, our data from human organoids indicates that the difference should be in the choroid, and not in the retina of the eye. Indeed, we find that DRAM2 KO cells from mouse choroid have a growth advantage compared with WT. Here we investigate the cell type composition of mouse choroid and identify putative genes responsible for the growth advantage in DRAM2 KO choroid cells.

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A systems biology approach uncovers novel disease mechanisms in age-related macular degeneration [human_retinal_organoid]

Project description:We have optimized CRISPR/Cas genome editing in human Embryonic Stem Cells (hESCs) and developed a method to generate hESC-derived eye organoids to investigate the cell type composition of these eye organoids using single cell RNA sequencing. We also investigate the consequences of the loss of a new AMD-associated gene, DRAM2, on the cell composition of the eye organoids.

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