Single cell transcriptome profiling of retinal ganglion cells identifies cellular subtypes

Bruce A. Rheaume, Amyeo Jereen, Mohan Bolisetty, Muhammad S. Sajid, Yue Yang, Kathleen Renna, Lili Sun, Paul Robson and Ephraim F. Trakhtenberg ()
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Bruce A. Rheaume: University of Connecticut School of Medicine
Amyeo Jereen: University of Connecticut School of Medicine
Mohan Bolisetty: The Jackson Laboratory for Genomic Medicine
Muhammad S. Sajid: University of Connecticut School of Medicine
Yue Yang: University of Connecticut School of Medicine
Kathleen Renna: University of Connecticut School of Medicine
Lili Sun: The Jackson Laboratory for Genomic Medicine
Paul Robson: The Jackson Laboratory for Genomic Medicine
Ephraim F. Trakhtenberg: University of Connecticut School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: Abstract Retinal ganglion cells (RGCs) convey the major output of information collected from the eye to the brain. Thirty subtypes of RGCs have been identified to date. Here, we analyze 6225 RGCs (average of 5000 genes per cell) from right and left eyes by single-cell RNA-seq and classify them into 40 subtypes using clustering algorithms. We identify additional subtypes and markers, as well as transcription factors predicted to cooperate in specifying RGC subtypes. Zic1, a marker of the right eye-enriched subtype, is validated by immunostaining in situ. Runx1 and Fst, the markers of other subtypes, are validated in purified RGCs by fluorescent in situ hybridization (FISH) and immunostaining. We show the extent of gene expression variability needed for subtype segregation, and we show a hierarchy in diversification from a cell-type population to subtypes. Finally, we present a website for comparing the gene expression of RGC subtypes.

Date: 2018
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DOI: 10.1038/s41467-018-05134-3

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