PUBLICATION
A unique macrophage subpopulation signals directly to progenitor cells to promote regenerative neurogenesis in the zebrafish spinal cord
- Authors
- Cavone, L., McCann, T., Drake, L.K., Aguzzi, E.A., Oprişoreanu, A.M., Pedersen, E., Sandi, S., Selvarajah, J., Tsarouchas, T.M., Wehner, D., Keatinge, M., Mysiak, K.S., Henderson, B.E.P., Dobie, R., Henderson, N.C., Becker, T., Becker, C.G.
- ID
- ZDB-PUB-210526-11
- Date
- 2021
- Source
- Developmental Cell 56(11): 1617-1630.e6 (Journal)
- Registered Authors
- Becker, Catherina G., Becker, Thomas, Mysiak, Karolina S.
- Keywords
- AP-1, HDAC1, TNFRSF1, macrophages, microglia, neural stem cells, regeneration, spinal cord
- MeSH Terms
-
- Animals
- Cell Lineage/genetics
- Gene Expression Regulation, Developmental/genetics
- Histone Deacetylase 1/genetics*
- Macrophages/cytology
- Macrophages/metabolism
- Neurogenesis/genetics*
- RNA-Seq
- Receptors, Tumor Necrosis Factor, Type I/genetics*
- Regeneration/genetics*
- Signal Transduction/genetics
- Single-Cell Analysis
- Spinal Cord/growth & development*
- Spinal Cord/metabolism
- Stem Cells/cytology
- Stem Cells/metabolism
- Transcription Factor AP-1/genetics
- Zebrafish/genetics
- Zebrafish Proteins/genetics*
- PubMed
- 34033756 Full text @ Dev. Cell
Citation
Cavone, L., McCann, T., Drake, L.K., Aguzzi, E.A., Oprişoreanu, A.M., Pedersen, E., Sandi, S., Selvarajah, J., Tsarouchas, T.M., Wehner, D., Keatinge, M., Mysiak, K.S., Henderson, B.E.P., Dobie, R., Henderson, N.C., Becker, T., Becker, C.G. (2021) A unique macrophage subpopulation signals directly to progenitor cells to promote regenerative neurogenesis in the zebrafish spinal cord. Developmental Cell. 56(11):1617-1630.e6.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping