ArticleNeuron2022
Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells.
Erratum issuedOpen access · greenAbstract read
In one paragraph
Article in Neuron, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 69 papers.
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69citing papers in PubMed
9.7field-weighted citation impact, top 1% of its field
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Who cites it
69 citing papers in PubMed, 115 citations in OpenAlex.
- Modulation of Presynaptic Inhibitory Retinal Circuits for Retinal Ganglion Cell Neuroprotection in Glaucoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- High Adhesion Superoleophobic Oil Microdroplets to Create Ocular Hypertension In Vivo.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Experimental upregulation of Lancl1 promotes axon regeneration after optic nerve injury in vivo.Experimental neurology · 2026Article
- Identification of a natively resilient but poorly regenerating retinal ganglion cell type in the G protein-coupled receptor 88-Cre transgenic mouse.Neural regeneration research · 2026Article
- Advances and applications of brain organoids in central nervous system disorders: Bridging the gap from laboratory to clinic.Neural regeneration research · 2026Article
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- Transcriptomic Analysis of Organotypic Porcine Retina Cultures.International journal of molecular sciences · 2026Article
- ATF4: Orchestrating Cellular Stress Adaptation, Metabolism, and Immune Regulation in Health and Disease.International journal of molecular sciences · 2026Review
- Transcriptional regulation of human NMNAT2: insights from 3D genome sequencing and bioinformatics.The FEBS journal · 2026Article
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- From Regeneration Failure to Functional Restoration: Unlocking the Neuronal-Intrinsic Regenerative Capacity as a Therapeutic Frontier for Optic Neuropathy and Glaucoma.CNS neuroscience & therapeutics · 2026Review
- Technological advances in axonal regeneration and structural plasticity: optogenetics, single-cell omics, and tissue clearing.Frontiers in cellular neuroscience · 2026Review
- Microtubule dynamics in adult retinal ganglion cells and dorsal root ganglion neurons.Frontiers in molecular neuroscience · 2026Article
- Article
- HDAC4 Promotes Neuroprotection of Retinal Ganglion Cells After Optic Nerve Injury.Investigative ophthalmology & visual science · 2025Article
- Absence of the axon initial segment in sensory neuron enhances resistance to amyotrophic lateral sclerosis.Brain : a journal of neurology · 2025Article
- Transcription factor activator protein 4 (AP4)-mediated intrinsic control of axon regeneration.Science advances · 2025Article
- OPTN protects retinal ganglion cells and ameliorates neuroinflammation in optic neuropathies.Communications biology · 2025Article
- Methods and applications of in vivo CRISPR screening.Nature reviews. Genetics · 2025Review
- Cutting-edge technologies in neural regeneration.Cell regeneration (London, England) · 2025Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
- Erratum issued
Authors and funding
27 authors at 2 institutions in 1 country.
Feng TianF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Yuyan ChengDepartments of Neurology, Psychiatry and Human Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1761, USA.
Songlin ZhouF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Qianbin WangF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Aboozar MonavarfeshaniF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
Kun GaoDepartments of Neurology, Psychiatry and Human Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1761, USA.
Weiqian JiangF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Riki KawaguchiDepartments of Neurology, Psychiatry and Human Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1761, USA.
Qing WangDepartments of Neurology, Psychiatry and Human Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1761, USA.
Mingjun TangF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Ryan DonahueF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Huyan MengF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Yu ZhangF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Anne JacobiF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
Wenjun YanDepartment of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
Jiani YinDepartments of Neurology, Psychiatry and Human Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1761, USA.
Xinyi CaiF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Zhiyun YangF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Shane HegartyF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Joanna StanickaF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Phillip DmitrievF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Daniel TaubF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Junjie ZhuF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Clifford J WoolfF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Joshua R SanesDepartment of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA. Electronic address: sanesj@mcb.harvard.edu.
Daniel H GeschwindDepartments of Neurology, Psychiatry and Human Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1761, USA. Electronic address: dhg@mednet.ucla.edu.
Zhigang HeF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: zhigang.he@childrens.harvard.edu.
Boston Children's Hospital · USHarvard University · US
Funding
SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI POMEROY, SCOTT LOREN · 1985 to 2015
$26.2MViral ModuleP30EY012196 · NEI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ZHIGANG HE · 1998 to 2026
$21.3MGenetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Hisashi Umemori · 2021 to 2026
$9.4MSOCS3 and optic nerve regenerationR01EY021526 · NEI · BOSTON CHILDREN'S HOSPITAL · PI HE, ZHIGANG · 2011 to 2020
$4.1MCRSIPR screening for novel regulators of retinal ganglion cell survival and axonal regenerationR01EY030204 · NEI · BOSTON CHILDREN'S HOSPITAL · PI HE, ZHIGANG, SANES, JOSHUA R · 2019 to 2023
$2.7MReprogramming Strategies of Promoting Optic Nerve Regeneration and Vision RestorationR01EY026939 · NEI · BOSTON CHILDREN'S HOSPITAL · PI HE, ZHIGANG · 2016 to 2020
$2.2MEpigenomic mechanisms regulating RGC survival and axon regenerationR00EY032181 · NEI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Feng Tian · 2024 to 2026
$750kCell type-specific vulnerability of neurons to axonal injury: comprehensive mapping of types and gene expression analyzed by high throughput single cell RNAseqR21NS104248 · NINDS · HARVARD UNIVERSITY · PI SANES, JOSHUA R · 2017 to 2018
$465kEpigenomic mechanisms regulating RGC survival and axon regenerationK99EY032181 · NEI · BOSTON CHILDREN'S HOSPITAL · PI TIAN, FENG · 2021 to 2023
$282kUncovering novel targets for retinal ganglion cell neuroprotection and axon regenerationF32EY031930 · NEI · BOSTON CHILDREN'S HOSPITAL · PI MONAVARFESHANI, ABOOZAR · 2020 to 2021
$134kTranscriptional signatures of glaucomatous retinal and optic nerve head cellsK99EY033457 · NEI · BOSTON CHILDREN'S HOSPITAL · PI MONAVARFESHANI, ABOOZAR · 2022 to 2022
$119kNEI NIH HHS F32 EY031930NEI NIH HHS K99 EY032181NEI NIH HHS K99 EY033457NEI NIH HHS P30 EY012196NEI NIH HHS R00 EY032181NEI NIH HHS R01 EY021526NEI NIH HHS R01 EY026939NEI NIH HHS R01 EY030204NICHD NIH HHS P30 HD018655NICHD NIH HHS P50 HD105351NINDS NIH HHS R21 NS104248
Abstract
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. Our results reveal core transcription programs that transform an initial axonal insult into a degenerative process and suggest novel strategies for treating neurodegenerative diseases.
Indexed as
Optic Nerve InjuriesRetinal Ganglion CellsAnimalsAxonsMiceMice, Inbred C57BLNerve RegenerationATF3ATF4axon regeneration and neuronal degenerationC/EBPgCHOPoptic nerveretinal ganglion cell
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