Journal
CELL REPORTS
Volume 31, Issue 9, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.107699
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Funding
- Swedish Childhood Cancer Fund
- Swedish Cancer Foundation
- Swedish Research Council
- Stockholm County Council (ALF projects)
- Frimurare Barnhus Foundation in Stockholm
- KI Foundation for Research
- Marta and Gunnar V Philipson Foundation
- Swedish Brain Foundation
- Swedish Board of Radiation Safety
- Jane and Dan Olsson Foundations
- Lars Hierta Memorial Foundation
- Tore Nilsons Stiftelse for Medicinsk Forskning
- Foundation Tornspiran
- Ake Wiberg Foundation
- O.E. och Edla Johanssons Vetenskapliga Stiftelse
- Olle Engkvist Foundation
- Regenerative Medicine Minnesota
- NIH [NS109770]
- Humor To Fight The Tumor
- L.B. & Terrie McKelvey
- Board of Research at the Karolinska Institutet
- Research Committee at the Karolinska University Hospital
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Cranial irradiation (IR), an effective tool to treat malignant brain tumors, triggers a chronic pro-inflammatory microglial response, at least in the adult brain. Using single-cell and bulk RNA sequencing, combined with histology, we show that the microglial response in the juvenile mouse hippocampus is rapid but returns toward normal within 1 week. The response is characterized by a series of temporally distinct homeostasis-, sensome-, and inflammation-related molecular signatures. We find that a single microglial cell simultaneously upregulates transcripts associated with pro- and anti-inflammatory microglial phenotypes. Finally, we show that juvenile and adult irradiated microglia are already transcriptionally distinct in the early phase after IR. Our results indicate that microglia are involved in the initial stages but may not be responsible for driving long-term inflammation in the juvenile brain.
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