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Feng Tian, PhD
Pronouns
He/Him/His
Job Title
Postdoc
Academic Rank
Research Fellow
Department
Neurosurgery
Authors
Feng Tian1,4, Yuyan Cheng2,4, Songlin Zhou1,4, Qianbin Wang1,4, Aboozar Monavarfeshani1,3, Kun Gao2, Weiqian Jiang1, Riki Kawaguchi2, Qing Wang2, Mingjun Tang1, Ryan Donahue1, Huyan Meng1, Yu Zhang1, Anne Jacobi1,3, Wenjun Yan3, Jiani Yin2, Xinyi Cai1, Zhiyun Yang1, Shane Hegarty1, Joanna Stanicka1, Phillip Dmitriev1, Daniel Taub1, Junjie Zhu1, Clifford J. Woolf1, Joshua R. Sanes3,5, Daniel H. Geschwind2,5 and Zhigang He1,5,6
Principal Investigator
Zhigang He
Research Category: Neurosciences
Tags
Regulatory programs governing neuronal death and regenerative failure in neurodegenerative diseases remain poorly understood. In adult mice, optic nerve crush (ONC) injury by severing retinal ganglion cell (RGCs) axons, results in massive RGC death and regenerative failure. We performed an in vivo CRISPR/Cas9-based genome-wide screen of 1893 transcription factors (TFs) to seek repressors of RGC survival and axon regeneration following ONC. In parallel, we profiled the epigenetic and transcriptional landscapes of injured RGCs by ATAC-seq and RNA-seq to identify injury responsive TFs and their targets. These analyses converged on four TFs as critical survival regulators, of which ATF3/CHOP preferentially regulate pathways activated by cytokines and innate immunity and ATF4/C/EBPγ regulate pathways engaged by intrinsic neuronal stressors. Manipulation of these TFs protects RGCs in a glaucoma model. Our results reveal core transcription programs that transform an initial axonal insult into a degenerative process and suggest novel strategies for treating neurodegenerative diseases.
Regulatory programs governing neuronal death and axon regeneration in neurodegenerative diseases remain poorly understood. In adult mice, optic nerve crush (ONC) injury by severing retinal ganglion cell (RGC) axons results in massive RGC death and regenerative failure. We performed an in vivo CRISPR-Cas9-based genome-wide screen of 1,893 transcription factors (TFs) to seek repressors of RGC survival and axon regeneration following ONC. In parallel, we profiled the epigenetic and transcriptional landscapes of injured RGCs by ATAC-seq and RNA-seq to identify injury-responsive TFs and their targets. These analyses converged on four TFs as critical survival regulators, of which ATF3/CHOP preferentially regulate pathways activated by cytokines and innate immunity and ATF4/C/EBPγ regulate pathways engaged by intrinsic neuronal stressors. Manipulation of these TFs protects RGCs in a glaucoma model.
