小柯机器人

美国西奈山伊坎医学院Panos Roussos，Gabriel E. Hoffman和Roman Kosoy共同合作，近期取得重要工作进展，他们报道人类小胶质细胞调节组的遗传学完善了阿尔茨海默病的风险基因位点。相关论文于2022年8月5日在线发表于《自然—遗传学》杂志上。

研究人员对来自150名供体的原代人类小胶质细胞进行了转录组和染色质可及性分析，以确定基因驱动的变异和细胞特异性增强子-启动子（E-P）的相互作用。综合精细映射分析确定了21个AD风险位点的潜在调控机制，其中18个被细化为单个基因，包括3个新的候选风险基因（KCNN4、FIBP和LRRC25）。转录因子调控网络捕获了AD风险变化，并将SPI1确定为小胶质细胞表达和AD风险的关键调控因子。这个捕捉人类小胶质细胞调节组变异的综合资源提供了对神经退行性疾病病因学的见解。

据介绍，小胶质细胞是在阿尔茨海默病（AD）的神经免疫和病因学中发挥关键作用的脑髓细胞，但其基因调控机制如何控制小胶质细胞的功能并促进AD的发生却知之甚少。

附：英文原文

Title: Genetics of the human microglia regulome refines Alzheimer’s disease risk loci

Author: Kosoy, Roman, Fullard, John F., Zeng, Biao, Bendl, Jaroslav, Dong, Pengfei, Rahman, Samir, Kleopoulos, Steven P., Shao, Zhiping, Girdhar, Kiran, Humphrey, Jack, de Paiva Lopes, Katia, Charney, Alexander W., Kopell, Brian H., Raj, Towfique, Bennett, David, Kellner, Christopher P., Haroutunian, Vahram, Hoffman, Gabriel E., Roussos, Panos

Issue&Volume: 2022-08-05

Abstract: Microglia are brain myeloid cells that play a critical role in neuroimmunity and the etiology of Alzheimer’s disease (AD), yet our understanding of how the genetic regulatory landscape controls microglial function and contributes to AD is limited. Here, we performed transcriptome and chromatin accessibility profiling in primary human microglia from 150 donors to identify genetically driven variation and cell-specific enhancer–promoter (E-P) interactions. Integrative fine-mapping analysis identified putative regulatory mechanisms for 21 AD risk loci, of which 18 were refined to a single gene, including 3 new candidate risk genes (KCNN4, FIBP and LRRC25). Transcription factor regulatory networks captured AD risk variation and identified SPI1 as a key putative regulator of microglia expression and AD risk. This comprehensive resource capturing variation in the human microglia regulome provides insights into the etiology of neurodegenerative disease. Transcriptomic and epigenomic profiling of human microglia identifies putative gene regulatory mechanisms for 21 Alzheimer’s disease (AD) risk loci. SPI1/PU.1 is nominated as a key regulator of microglia gene expression and AD risk.

DOI: 10.1038/s41588-022-01149-1

Source:https://www.nature.com/articles/s41588-022-01149-1

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex