Localized EMT reprograms glial progenitors to promote spinal cord repair
| Autor: | Anthony R. McAdow, Dana Klatt Shaw, Lili Zhou, Brooke Burris, Samantha A. Morris, Mayssa H. Mokalled, Sabine Dietmann, Vishnu Muraleedharan Saraswathy, E. Butka |
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| Rok vydání: | 2021 |
| Předmět: |
Spinal Cord Regeneration
Epithelial-Mesenchymal Transition Gene regulatory network Regenerative medicine Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Gene expression medicine Animals Progenitor cell Molecular Biology Spinal cord injury Zebrafish Spinal Cord Injuries Cell Proliferation 030304 developmental biology Mammals Neurons 0303 health sciences biology Regeneration (biology) fungi Cell Differentiation Cell Biology Zebrafish Proteins medicine.disease Spinal cord biology.organism_classification Cell biology medicine.anatomical_structure Spinal Cord nervous system embryonic structures Neuroglia 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Dev Cell |
| ISSN: | 1534-5807 |
| Popis: | Anti-regenerative scarring obstructs spinal cord repair in mammals and presents a major hurdle for regenerative medicine. In contrast, adult zebrafish possess specialized glial cells that spontaneously repair spinal cord injuries by forming a pro-regenerative bridge across the severed tissue. To identify the mechanisms that regulate differential regenerative capacity between mammals and zebrafish, we first defined the molecular identity of zebrafish bridging glia and then performed cross-species comparisons with mammalian glia. Our transcriptomics show that pro-regenerative zebrafish glia activate an epithelial-to-mesenchymal transition (EMT) gene program and that EMT gene expression is a major factor distinguishing mammalian and zebrafish glia. Functionally, we found that localized niches of glial progenitors undergo EMT after spinal cord injury in zebrafish and, using large-scale CRISPR-Cas9 mutagenesis, we identified the gene regulatory network that activates EMT and drives functional regeneration. Thus, non-regenerative mammalian glia lack an essential EMT-driving gene regulatory network that reprograms pro-regenerative zebrafish glia after injury. |
| Databáze: | OpenAIRE |
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