Single cell transcriptome profiling of retinal ganglion cells identifies cellular subtypes

A team of researchers identified molecular differences between retinal ganglion cell subtypes, information which could lead to a better understanding as to why some respond differently to injury or treatments.

The new study, published this week in Nature Communications, identifies 40 subtypes of retinal ganglion cells, which convey visual data from the eye to the brain, along with the genetic markers and transcription factors that differentiate them.

“This knowledge could help develop more effective therapeutics to treat optic neuropathies and glaucoma,” says Ephraim F. Trakhtenberg, of UConn Health’s Department of Neuroscience, who led the research team, which included Paul Robson, director of single-cell biology at The Jackson Laboratory (JAX).

Single-cell RNA sequencing technologies are filling in fine details in the catalog of life. Researchers can now isolate single cells and amplify their genetic material to probe their full complement of RNA. This makes it possible to conduct a detailed census of cells of a given type, identifying subtle molecular differences that constitute subtypes.

Prior to this study, 30 subtypes of retinal ganglion cells had been identified. The research team selected them precisely because more of its subtypes have been identified to date compared to any other major neuronal cell type.

In addition to identifying new subtypes and their markers, the researchers demonstrate the amount of gene expression variability between cells needed to differentiate them into subtypes, and present a hierarchy from a cell type population to subtypes. The datasets for the study are publicly available through a user-friendly UConn Health web application, RGC Subtypes Gene Browser.

Global properties of subtype transcriptome and the known RGC markers

rna-seq

a Violin graph showing average number and distribution of genes expressed per cluster as probability density. b Proportion of genes number expressed across different ranges, from low to highly expressed genes. c, d Percent of RGCs per cluster (c) and color-coded predominance of the cluster in left (red) or right (blue) eye (d). Subtypes 1 and 13 indicated by arrowheads in (ac) are the lighter intensity boxes in (b) at the 1 NE threshold. e Heatmap of the known RGC markers shows that Tubb3, RBPMS, and Sox4 have the most homogenous expression across all RGC subtypes. Most of the known RGC markers show strong expression in more than one cluster

Availability – RGC subtypes gene browser https://health.uconn.edu/neuroregeneration-lab/rgc-subtypes-gene-browser

Rheaume BA, Jereen A, Bolisetty M, Sajid MS, Yang Y, Renna K, Sun L, Robson P, Trakhtenberg EF. (2018) Single cell transcriptome profiling of retinal ganglion cells identifies cellular subtypes. Nat Commun 9(1):2759. [article]

Source – UCONN

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