小胶质细胞
转录组
DNA甲基化
生物
人脑
甲基化
表观遗传学
情绪障碍
神经科学
基因表达
遗传学
基因
医学
免疫学
炎症
精神科
焦虑
作者
Lot de Witte,Zhaoyu Wang,Gijsje Snijders,Natalia Mendelev,Qingkun Liu,Marjolein Sneeboer,Marco P. Boks,Yongchao Ge,Fatemeh Haghighi
标识
DOI:10.1016/j.biopsych.2021.10.020
摘要
BackgroundTranscriptome studies have revealed age-, disease-, and region-associated microglial phenotypes reflecting changes in microglial function during development, aging, central nervous system homeostasis, and pathology. The molecular mechanisms that contribute to these transcriptomic changes are largely unknown. The aim of this study was to characterize the DNA methylation landscape of human microglia and the factors that contribute to variations in the microglia methylome. We hypothesized that both age and brain region would have a large impact on DNA methylation in microglia.MethodsMicroglia from postmortem brain tissue of four different brain regions of 22 donors, encompassing 1 patient with schizophrenia, 13 patients with mood disorder pathology, and 8 control subjects, were isolated and assayed using a genome-wide methylation array.ResultsWe found that human microglial cells have a methylation profile distinct from bulk brain tissue and neurons, and age explained a considerable part of the variation. Additionally, we showed that interindividual factors had a much larger effect on the methylation landscape of microglia than brain region, which was also seen at the transcriptome level. In our exploratory analysis, we found various differentially methylated regions that were related to disease status (mood disorder vs. control). This included differentially methylated regions that are linked to gene expression in microglia, as well as to myeloid cell function or neuropsychiatric disorders.ConclusionsAlthough based on relatively small samples, these findings suggest that the methylation profile of microglia is responsive to interindividual variations and thereby plays an important role in the heterogeneity of microglia observed at the transcriptome level.
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