A unique macrophage subpopulation signals directly to progenitor cells to promote regenerative neurogenesis in the zebrafish spinal cord
| Autor: | Tess McCann, Marcus Keatinge, Leonardo Cavone, Beth E. P. Henderson, Karolina S. Mysiak, Louisa K. Drake, Themistoklis M. Tsarouchas, Soe Sandi, Erika A. Aguzzi, Ana-Maria Oprişoreanu, Jathurshan Selvarajah, Ross Dobie, Elisa Pedersen, Neil C. Henderson, Catherina G. Becker, Thomas Becker, Daniel Wehner |
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| Rok vydání: | 2021 |
| Předmět: |
Neurogenesis
Central nervous system Histone Deacetylase 1 Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine medicine Animals Regeneration Cell Lineage RNA-Seq Progenitor cell Molecular Biology Zebrafish 030304 developmental biology 0303 health sciences Innate immune system Microglia Macrophages Stem Cells Regeneration (biology) Gene Expression Regulation Developmental Cell Biology Zebrafish Proteins biology.organism_classification Neural stem cell Cell biology Transcription Factor AP-1 medicine.anatomical_structure Spinal Cord Receptors Tumor Necrosis Factor Type I Single-Cell Analysis 030217 neurology & neurosurgery Signal Transduction Developmental Biology |
| Zdroj: | Developmental Cell. 56:1617-1630.e6 |
| ISSN: | 1534-5807 |
| Popis: | Central nervous system injury re-initiates neurogenesis in anamniotes (amphibians and fishes), but not in mammals. Activation of the innate immune system promotes regenerative neurogenesis, but it is fundamentally unknown whether this is indirect through the activation of known developmental signaling pathways or whether immune cells directly signal to progenitor cells using mechanisms that are unique to regeneration. Using single-cell RNA-seq of progenitor cells and macrophages, as well as cell-type-specific manipulations, we provide evidence for a direct signaling axis from specific lesion-activated macrophages to spinal progenitor cells to promote regenerative neurogenesis in zebrafish. Mechanistically, TNFa from pro-regenerative macrophages induces Tnfrsf1a-mediated AP-1 activity in progenitors to increase regeneration-promoting expression of hdac1 and neurogenesis. This establishes the principle that macrophages directly communicate to spinal progenitor cells via non-developmental signals after injury, providing potential targets for future interventions in the regeneration-deficient spinal cord of mammals. |
| Databáze: | OpenAIRE |
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