Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease

被引：510

作者：

Chen, Wei-Ting ^{[1
,2
]}

Lu, Ashley ^{[1
,2
]}

Craessaerts, Katleen ^{[1
,2
]}

Pavie, Benjamin ^{[1
,2
,3
,4
]}

Frigerio, Carlo Sala ^{[1
,2
,10
]}

Corthout, Nikky ^{[1
,2
,3
,4
]}

Qian, Xiaoyan ^{[5
]}

Lalakova, Jana ^{[5
]}

Kuhnemund, Malte ^{[5
]}

Voytyuk, Iryna ^{[1
,2
]}

Wolfs, Leen ^{[1
,2
]}

Mancuso, Renzo ^{[1
,2
]}

Salta, Evgenia ^{[1
,2
]}

Balusu, Sriram ^{[1
,2
]}

Snellinx, An ^{[1
,2
]}

Munck, Sebastian ^{[1
,2
,3
,4
]}

Jurek, Aleksandra ^{[6
]}

Navarro, Jose Fernandez ^{[6
]}

Saido, Takaomi C. ^{[7
]}

Huitinga, Inge ^{[8
,9
]}

Lundeberg, Joakim ^{[6
]}

Fiers, Mark ^{[1
,2
,10
]}

De Strooper, Bart ^{[1
,2
,10
]}

机构：

[1] VIB Ctr Brain & Dis Res, B-3000 Leuven, Belgium

[2] Katholieke Univ Leuven, Dept Neurosci, Leuven Brain Inst, B-3000 Leuven, Belgium

[3] VIB Bio Imaging Core, B-9052 Ghent, Belgium

[4] VIB Bio Imaging Core, B-3000 Leuven, Belgium

[5] Cartana AB, Nobels Vag 16, S-17165 Solna, Sweden

[6] KTH Royal Inst Technol, Dept Gene Technol, Sci Life Lab, S-17121 Stockholm, Sweden

[7] RIKEN Brain Sci Inst, Lab Proteolyt Neurosci, Wako, Saitama 3510198, Japan

[8] Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Dept Neuroimmunol, NL-1105 BA Amsterdam, Netherlands

[9] Univ Amsterdam, Swammerdam Inst Life Sci, NL-1098 XH Amsterdam, Netherlands

[10] UCL, UK Dementia Res Inst, London WC1E 6BT, England

来源：

CELL | 2020年 / 182卷 / 04期

基金：

欧洲研究理事会;

关键词：

GENE-EXPRESSION; A-BETA; COGNITIVE DECLINE; GENOMIC ANALYSIS; HUMAN BRAIN; CELL-TYPES; COMPLEMENT; MICROGLIA; TISSUE; PATHWAY;

D O I：

10.1016/j.cell.2020.06.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-mu m 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.

引用

页码：976 / +

页数：35

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