Disease-associated astrocytes in Alzheimer's disease and aging

被引：552

作者：

Habib, Naomi ^{[1
,2
]}

McCabe, Cristin ^{[2
]}

Medina, Sedi ^{[3
]}

Varshavsky, Miriam ^{[1
]}

Kitsberg, Daniel ^{[1
]}

Dvir-Szternfeld, Raz ^{[3
]}

Green, Gilad ^{[1
]}

Dionne, Danielle ^{[2
]}

Nguyen, Lan ^{[2
]}

Marshall, Jamie L. ^{[2
]}

Chen, Fei ^{[2
]}

Zhang, Feng ^{[2
,4
,5
]}

Kaplan, Tommy ^{[6
]}

Regev, Aviv ^{[2
,7
]}

Schwartz, Michal ^{[2
,3
]}

机构：

[1] Hebrew Univ Jerusalem, Edmond & Lily Safra Ctr Brain Sci, Jerusalem, Israel

[2] Broad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA 02142 USA

[3] Weizmann Inst Sci, Dept Neurobiol, Rehovot, Israel

[4] MIT, Howard Hughes Med Inst, McGovern Inst Brain Res, Dept Brain & Cognit Sci, Cambridge, MA USA

[5] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[6] Hebrew Univ Jerusalem, Sch Comp Sci & Engn, Jerusalem, Israel

[7] MIT, Howard Hughes Med Inst, Koch Inst Integrat Canc Res, Dept Biol, Cambridge, MA USA

来源：

NATURE NEUROSCIENCE | 2020年 / 23卷 / 06期

基金：

欧洲研究理事会; 以色列科学基金会;

关键词：

NUCLEUS RNA-SEQ; EXPRESSION; PATHOLOGY; BETA;

D O I：

10.1038/s41593-020-0624-8

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The role of non-neuronal cells in Alzheimer's disease progression has not been fully elucidated. Using single-nucleus RNA sequencing, we identified a population of disease-associated astrocytes in an Alzheimer's disease mouse model. These disease-associated astrocytes appeared at early disease stages and increased in abundance with disease progression. We discovered that similar astrocytes appeared in aged wild-type mice and in aging human brains, suggesting their linkage to genetic and age-related factors. A new subset of disease-associated astrocytes (DAAs) is identified in a mouse model of Alzheimer's disease by single-nucleus RNA sequencing. DAAs are also found in aged wild-type mice, suggesting a link to genetic and age-related factors.

引用

页码：701 / +

页数：25

共 35 条

[1] destiny: diffusion maps for large-scale single cell data in R [J].

Angerer, Philipp ;

Haghverdi, Laleh ;

Buettner, Maren ;

Theis, Fabian J. ;

Marr, Carsten ;

Buettner, Florian .

BIOINFORMATICS, 2016, 32 (08) :1241-1243

[2] PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease [J].

Baruch, Kuti ;

Deczkowska, Aleksandra ;

Rosenzweig, Neta ;

Tsitsou-Kampeli, Afroditi ;

Sharif, Alaa Mohammad ;

Matcovitch-Natan, Orit ;

Kertser, Alexander ;

David, Eyal ;

Amit, Ido ;

Schwartz, Michal .

NATURE MEDICINE, 2016, 22 (02) :135-137

[3] Breaking immune tolerance by targeting Foxp3+ regulatory T cells mitigates Alzheimer's disease pathology [J].

Baruch, Kuti ;

Rosenzweig, Neta ;

Kertser, Alexander ;

Deczkowska, Aleksandra ;

Sharif, Alaa Mohammad ;

Spinrad, Amit ;

Tsitsou-Kampeli, Afroditi ;

Sarel, Ayelet ;

Cahalon, Liora ;

Schwartz, Michal .

NATURE COMMUNICATIONS, 2015, 6

[4] Chronic gliosis triggers Alzheimer's disease-like processing of amyloid precursor protein [J].

Bates, KA ;

Fonte, J ;

Robertson, TA ;

Martins, RN ;

Harvey, AR .

NEUROSCIENCE, 2002, 113 (04) :785-796

[5] Integrating single-cell transcriptomic data across different conditions, technologies, and species [J].

Butler, Andrew ;

Hoffman, Paul ;

Smibert, Peter ;

Papalexi, Efthymia ;

Satija, Rahul .

NATURE BIOTECHNOLOGY, 2018, 36 (05) :411-+

[6] Normal aging induces A1-like astrocyte reactivity [J].

Clarke, Laura E. ;

Liddelow, Shane A. ;

Chakraborty, Chandrani ;

Munch, Alexandra E. ;

Heiman, Myriam ;

Barres, Ben A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (08) :E1896-E1905

[7] The Cellular Phase of Alzheimer's Disease [J].

De Strooper, Bart ;

Karran, Eric .

CELL, 2016, 164 (04) :603-615

[8] Nuclei multiplexing with barcoded antibodies for single-nucleus genomics [J].

Gaublomme, Jellert T. ;

Li, Bo ;

McCabe, Cristin ;

Knecht, Abigail ;

Yang, Yiming ;

Drokhlyansky, Eugene ;

Van Wittenberghe, Nicholas ;

Waldman, Julia ;

Dionne, Danielle ;

Nguyen, Lan ;

De Jager, Philip L. ;

Yeung, Bertrand ;

Zhao, Xinfang ;

Habib, Naomi ;

Rozenblatt-Rosen, Orit ;

Regev, Aviv .

NATURE COMMUNICATIONS, 2019, 10 (1)

[9] A single-cell survey of the small intestinal epithelium [J].

Haber, Adam L. ;

Biton, Moshe ;

Rogel, Noga ;

Herbst, Rebecca H. ;

Shekhar, Karthik ;

Smillie, Christopher ;

Burgin, Grace ;

Delorey, Toni M. ;

Howitt, Michael R. ;

Katz, Yarden ;

Tirosh, Itay ;

Beyaz, Semir ;

Dionne, Danielle ;

Zhang, Mei ;

Raychowdhury, Raktima ;

Garrett, Wendy S. ;

Rozenblatt-Rosen, Orit ;

Shi, Hai Ning ;

Yilmaz, Omer ;

Xavier, Ramnik J. ;

Regev, Aviv .

NATURE, 2017, 551 (7680) :333-+

[10]

Habib N, 2017, NAT METHODS, V14, P955, DOI [10.1038/NMETH.4407, 10.1038/nmeth.4407]

← 1 2 3 4 →