Multi-species single-cell transcriptomic analysis of ocular compartment regulons

We constructed the first single cell atlas of the human, porcine and zebrafish ocular compartments and compared inter-species transcriptomic expression data in retinal cell populations. In the non-retinal cell populations, we identified putative adult stem cells present in the iris tissue. We created a disease map of genes involved in eye disorders across cells of posterior and anterior compartments of eye. We also probed the regulons of different cell populations, which included transcription factors (TFs) and receptor-ligand interactions and reveal unique directional signalling and cross-talks between ocular cell-types. Such regulons were checked for conservation across vertebrates including human, mouse, pig, zebrafish, and non-human primates to identify common core factors. Finally, we focused on one such transcription factor KLF7, which was conserved across species. After perturbing KLF7 gene expression during retinal ganglion cells (RGC) differentiation from human embryonic stem cells, we conclude that KLF7 plays a major role in maturation of RGC cells during differentiation. Overall design: Single cell RNAseq of different celltypes of eye was done and transcription factor profiles were studied.