TY - JOUR T1 - Cross-species transcriptomic and epigenomic analysis reveals key regulators of injury response and neuronal regeneration in vertebrate retinas JF - bioRxiv DO - 10.1101/717876 SP - 717876 AU - Thanh Hoang AU - Jie Wang AU - Patrick Boyd AU - Fang Wang AU - Clayton Santiago AU - Lizhi Jiang AU - Manuela Lahne AU - Levi J. Todd AU - Cristian Saez AU - Sooyeon Yoo AU - Casey Keuthan AU - Isabella Palazzo AU - Natalie Squires AU - Warren A. Campbell AU - Meng Jia AU - Fatemeh Rajaii AU - Trisha Payail AU - Guohua Wang AU - John Ash AU - Andy J. Fischer AU - David R. Hyde AU - Jiang Qian AU - Seth Blackshaw Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/07/31/717876.abstract N2 - Injury induces retinal Müller glia of cold-blooded, but not mammalian, vertebrates to generate neurons. To identify gene regulatory networks that control neuronal reprogramming in retinal glia, we comprehensively profiled injury-dependent changes in gene expression and chromatin conformation in Müller glia from zebrafish, chick and mice using bulk RNA and ATAC-Seq, as well as single-cell RNA-Seq. Cross-species integrative analysis of these data, together with functional validation of candidate genes, identified evolutionarily conserved and species-specific gene networks controlling glial quiescence, gliosis and neurogenesis. In zebrafish and chick, transition from quiescence to gliosis is a critical stage in acquisition of neurogenic competence, while in mice a dedicated network suppresses this transition and rapidly restores quiescence. Selective disruption of NFI family transcription factors, which maintain and restore quiescence, enables Müller glia to proliferate and robustly generate neurons in adult mice after retinal injury. These comprehensive resources and findings will facilitate the design of cell-based therapies aimed at restoring retinal neurons lost to degenerative disease. ER -