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空间转录组学和原位测序可剖析阿尔茨海默氏病
作者:小柯机器人 发布时间:2020/7/26 20:29:30

比利时鲁汶大学Bart De Strooper、Mark Fiers等研究人员合作利用空间转录组学和原位测序剖析了阿尔茨海默氏病。相关论文于2020年7月22日在线发表于《细胞》。

在阿尔茨海默氏病(AD)小鼠模型中,研究人员使用空间转录组学在淀粉样斑块周围直径100μm的组织域中检测了转录变化。研究人员证明了丰富的髓鞘和少突胶质细胞基因(OLIG)共表达网络的早期改变,而斑块诱导基因(PIG)的多细胞基因共表达网络涉及补体系统、氧化应激、溶酶体和炎症,这些在疾病后期尤为突出。

研究人员使用小鼠和人脑切片上的原位测序证实了在细胞水平上观察到的大多数变化。全基因组空间转录组学分析提供了一种前所未有的方法,来解开AD和其他脑部疾病的致病标志附近细胞网络失调。

据悉,尽管在AD的淀粉样斑块周围观察到复杂的炎症样变化,但对于这种反应的特征性分子变化和细胞相互作用知之甚少。

附:英文原文

Title: Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease

Author: Wei-Ting Chen, Ashley Lu, Katleen Craessaerts, Benjamin Pavie, Carlo Sala Frigerio, Nikky Corthout, Xiaoyan Qian, Jana Laláková, Malte Kühnemund, Iryna Voytyuk, Leen Wolfs, Renzo Mancuso, Evgenia Salta, Sriram Balusu, An Snellinx, Sebastian Munck, Aleksandra Jurek, Jose Fernandez Navarro, Takaomi C. Saido, Inge Huitinga, Joakim Lundeberg, Mark Fiers, Bart De Strooper

Issue&Volume: 2020-07-22

Abstract: Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer’s disease (AD), little is known about the molecular changes and cellular interactions that characterize this response. We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-μm diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.

DOI: 10.1016/j.cell.2020.06.038

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30815-1

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/