TY - JOUR
T1 - Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease
AU - Chen, Wei-Ting
AU - Lu, Ashley
AU - Craessaerts, Katleen
AU - Pavie, Benjamin
AU - Sala Frigerio, Carlo
AU - Corthout, Nikky
AU - Qian, Xiaoyan
AU - Laláková, Jana
AU - Kühnemund, Malte
AU - Voytyuk, Iryna
AU - Wolfs, Leen
AU - Mancuso, Renzo
AU - Salta, Evgenia
AU - Balusu, Sriram
AU - Snellinx, An
AU - Munck, Sebastian
AU - Jurek, Aleksandra
AU - Fernandez Navarro, Jose
AU - Saido, Takaomi C
AU - Huitinga, Inge
AU - Lundeberg, Joakim
AU - Fiers, Mark
AU - De Strooper, Bart
N1 - Copyright © 2020 Elsevier Inc. All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1016/j.cell.2020.06.038
DO - 10.1016/j.cell.2020.06.038
M3 - Article
C2 - 32702314
VL - 182
SP - 976
EP - 991
JO - Cell
JF - Cell
SN - 0092-8674
ER -