Spatial transcriptomics and in situ sequencing to study Alzheimer’s disease
Authors list
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 StrooperAbstract
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.
Journal details
Journal Cell
Volume 182
Issue number 4
Pages 976-991.e19
Available online
Publication date
Full text links
Publisher website (DOI) 10.1016/j.cell.2020.06.038
Europe PubMed Central 32702314
Pubmed 32702314
Keywords
Type of publication