Department of Women's and Children's Health, Karolinska Institutet, 171 64 Stockholm, Sweden.
Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Cell Rep. 2020 Jun 2;31(9):107699. doi: 10.1016/j.celrep.2020.107699.
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.
颅照射（IR）是治疗恶性脑肿瘤的有效手段，至少在成年脑中会引发慢性促炎小胶质细胞反应。我们使用单细胞和批量 RNA 测序，结合组织学，显示幼年小鼠海马中的小胶质细胞反应迅速，但在 1 周内恢复正常。该反应的特征是一系列具有时间差异的稳态、传感和炎症相关分子特征。我们发现单个小胶质细胞同时上调与促炎和抗炎小胶质细胞表型相关的转录本。最后，我们发现幼年和成年受照射的小胶质细胞在 IR 后早期就已经在转录上有所不同。我们的研究结果表明，小胶质细胞参与了初始阶段，但可能不是导致幼年大脑长期炎症的原因。
