A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease

被引：3455

作者：

Keren-Shaul, Hadas ^{[1
]}

Spinrad, Amit ^{[1
,2
]}

Weiner, Assaf ^{[1
,3
,4
]}

Matcovitch-Natan, Orit ^{[1
,2
]}

Dvir-Szternfeld, Raz ^{[2
]}

Ulland, Tyler K. ^{[5
]}

David, Eyal ^{[1
]}

Baruch, Kuti ^{[2
]}

Lara-Astaiso, David ^{[1
]}

Toth, Beata ^{[6
]}

Itzkovitz, Shalev ^{[6
]}

Colonna, Marco ^{[5
]}

Schwartz, Michal ^{[2
]}

Amit, Ido ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Immunol, IL-7610001 Rehovot, Israel

[2] Weizmann Inst Sci, Dept Neurobiol, IL-7610001 Rehovot, Israel

[3] Royal Netherlands Acad Arts & Sci, Hubrecht Inst KNAW, NL-3584 CG Utrecht, Netherlands

[4] Univ Med Ctr, Canc Genom Netherlands, NL-3584 CG Utrecht, Netherlands

[5] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA

[6] Weizmann Inst Sci, Dept Mol Cell Biol, IL-7610001 Rehovot, Israel

来源：

CELL | 2017年 / 169卷 / 07期

基金：

欧洲研究理事会; 以色列科学基金会;

关键词：

CELL RNA-SEQ; GENE-EXPRESSION SIGNATURE; CENTRAL-NERVOUS-SYSTEM; SINGLE-CELL; MOUSE MODEL; TREM2; VARIANTS; NEURODEGENERATIVE DISEASE; REGULATORY LANDSCAPE; P2Y(12) RECEPTOR; PLAQUE-FORMATION;

D O I：

10.1016/j.cell.2017.05.018

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：

Alzheimer's disease (AD) is a detrimental neurodegenerative disease with no effective treatments. Due to cellular heterogeneity, defining the roles of immune cell subsets in AD onset and progression has been challenging. Using transcriptional single-cell sorting, we comprehensively map all immune populations in wild-type and AD-transgenic (Tg-AD) mouse brains. We describe a novel microglia type associated with neurodegenerative diseases (DAM) and identify markers, spatial localization, and pathways associated with these cells. Immunohistochemical staining of mice and human brain slices shows DAM with intracellular/phagocytic A beta particles. Single-cell analysis of DAM in Tg-AD and triggering receptor expressed on myeloid cells 2 (Trem2)(-/-) Tg-AD reveals that the DAM program is activated in a two-step process. Activation is initiated in a Trem2-independent manner that involves downregulation of microglia checkpoints, followed by activation of a Trem2-dependent program. This unique microglia-type has the potential to restrict neurodegeneration, which may have important implications for future treatment of AD and other neurodegenerative diseases.

引用

页码：1276 / +

页数：32

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