Mapping developmental trajectories and subtype diversity of normal and glaucomatous human retinal ganglion cells by single ‐cell transcriptome analysis

Single ‐cell transcriptome‐based developmental trajectories reveal developmental abnormalities in glaucoma patient‐specific retinal ganglion cells (RGCs). A comparison of the developmental trajectories, based on lineage‐ and stage‐specific transcriptional signature of differentiating glaucoma pat ient (SIX6risk allele) ‐specific and control induced pluripotent stem cells along the RGC lineage, revealed that theSIX6risk allele RGCs are compromised in mature phenotype and subtype composition, including those that are degeneration ‐resistant vs controls. AbstractGlaucoma is characterized by a progressive degeneration of retinal ganglion cells (RGCs), leading to irreversible vision loss. Currently, there is no effective treatment for RGC degeneration. We are using a disease in a dish stem cell model to examine the developmental susceptibility of RGCs to glaucomatous degeneration, which may inform on the formulation of therapeutic approaches. Here, we used single ‐cell transcriptome analysis ofSIX6 risk allele (SIX6risk allele) primary open angle glaucoma patient ‐specific and control hRGCs to compare developmental trajectories in terms of lineage‐ and stage‐specific transcriptional signature to identify dysregulated stages/genes, and subtype composition to estimate the relative vulnerability of RGCs to degeneration because their ability to regenerate axons are subtype‐specific. The developmental trajectories, beginning from neural stem cells to RGCs, were ...

Source: Stem Cells - June 17, 2020 Category: Stem Cells Authors: Pooja Teotia, Meng Niu, Iqbal Ahmad Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research