当前位置: X-MOL 学术Nat. Med. › 论文详情
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease
Nature Medicine ( IF 30.641 ) Pub Date : 2020-01-13 , DOI: 10.1038/s41591-019-0695-9
Yingyue Zhou; Wilbur M. Song; Prabhakar S. Andhey; Amanda Swain; Tyler Levy; Kelly R. Miller; Pietro L. Poliani; Manuela Cominelli; Shikha Grover; Susan Gilfillan; Marina Cella; Tyler K. Ulland; Konstantin Zaitsev; Akinori Miyashita; Takeshi Ikeuchi; Makoto Sainouchi; Akiyoshi Kakita; David A. Bennett; Julie A. Schneider; Michael R. Nichols; Sean A. Beausoleil; Jason D. Ulrich; David M. Holtzman; Maxim N. Artyomov; Marco Colonna

Glia have been implicated in Alzheimer’s disease (AD) pathogenesis. Variants of the microglia receptor triggering receptor expressed on myeloid cells 2 (TREM2) increase AD risk, and activation of disease-associated microglia (DAM) is dependent on TREM2 in mouse models of AD. We surveyed gene-expression changes associated with AD pathology and TREM2 in 5XFAD mice and in human AD by single-nucleus RNA sequencing. We confirmed the presence of Trem2-dependent DAM and identified a previously undiscovered Serpina3n+C4b+ reactive oligodendrocyte population in mice. Interestingly, remarkably different glial phenotypes were evident in human AD. Microglia signature was reminiscent of IRF8-driven reactive microglia in peripheral-nerve injury. Oligodendrocyte signatures suggested impaired axonal myelination and metabolic adaptation to neuronal degeneration. Astrocyte profiles indicated weakened metabolic coordination with neurons. Notably, the reactive phenotype of microglia was less evident in TREM2-R47H and TREM2-R62H carriers than in non-carriers, demonstrating a TREM2 requirement in both mouse and human AD, despite the marked species-specific differences.
更新日期:2020-01-14

 

全部期刊列表>>
2020新春特辑
限时免费阅读临床医学内容
ACS材料视界
科学报告最新纳米科学与技术研究
清华大学化学系段昊泓
自然科研论文编辑服务
中国科学院大学楚甲祥
中国科学院微生物研究所潘国辉
中国科学院化学研究所
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug