GSE118780
Transcriptomic Signatures of Postnatal and Adult Intrinsically Photosensitive Ganglion Cells
Purpose: The goal of this study was to determine a “molecular parts list” for intrinsically photosensitive retinal ganglion cells (ipRGCs), which are rare mammalian photoreceptors essential for non-image-forming vision functions, such as circadian photoentrainment and the pupillary light reflex. Methods: We conducted a thorough unbiased transcriptomic analysis of ipRGCs by purifying GFP-tagged ipRGCs through a combination of FACS and immunoaffinity and comparing this the transcriptional profile of GFP-negative RGCs. We did this in two different mouse lines, marking partially overlapping subsets of ipRGCs. One was a BAC transgenic reporter (Opn4-GFP), which fluorescently labels M1-M3 ipRGCs and the other was a Opn4-Cre;Z/EG reporter system, which labels all ipRGC subtypes, M1-M6 Results: We find dozens of novel genes highly enriched in ipRGCs. We reveal that Rasgrp1 and Tbx20 are selectively expressed in subsets of ipRGCs, though these molecularly defined groups imperfectly match established ipRGC subtypes. We demonstrate that the ipRGCs regulating circadian photoentrainment are unexpectedly diverse at the molecular level. Conclusions: Our study represents the first detailed analysis of ipRGC transcriptomes by RNA-seq. Our findings reveal unexpected complexity in gene expression patterns across mammalian ipRGC subtypes. Overall design: We conducted a thorough unbiased transcriptomic analysis of ipRGCs by purifying GFP-tagged ipRGCs through a combination of FACS and immunoaffinity and comparing this the transcriptional profile of GFP-negative RGCs. We did this in two different mouse lines, marking partially overlapping subsets of ipRGCs. One was a BAC transgenic reporter (Opn4-GFP), which fluorescently labels M1-M3 ipRGCs and the other was a Opn4-Cre;Z/EG reporter system, which labels all ipRGC subtypes, M1-M6