An inducible genetic tool to track and manipulate specific microglial states reveals their plasticity and roles in remyelination

被引：22

作者：

Barclay, Kia M. ^{[1
,2
,3
,4
]}

Abduljawad, Nora ^{[1
,2
,3
,4
,5
]}

Cheng, Zuolin ^{[6
]}

Kim, Min Woo ^{[3
,4
,5
,7
,8
]}

Zhou, Lu ^{[1
,3
,4
]}

Yang, Jin ^{[1
,3
,4
]}

Rustenhoven, Justin ^{[3
,4
,5
]}

Mazzitelli, Jose A. ^{[2
,3
,4
,5
,8
]}

Smyth, Leon C. D. ^{[3
,4
,5
]}

Kapadia, Dvita ^{[1
]}

Brioschi, Simone ^{[5
]}

Beatty, Wandy ^{[9
]}

Hou, Jinchao ^{[3
,4
,5
]}

Saligrama, Naresha ^{[3
,4
,5
,10
,11
]}

Colonna, Marco ^{[3
,4
,5
]}

Yu, Guoqiang ^{[6
]}

Kipnis, Jonathan ^{[3
,4
,5
]}

Li, Qingyun ^{[1
,3
,4
,12
]}

机构：

[1] Washington Univ St Louis, Louis Sch Med, Dept Neurosci, St Louis, MO 63110 USA

[2] Washington Univ, Neurosci Grad Program, Sch Med, St Louis, MO 63110 USA

[3] Washington Univ, Hope Ctr Neurol Disorders, Sch Med, St Louis, MO 63110 USA

[4] Washington Univ, Brain Immunol & Glia BIG Ctr, Sch Med, St Louis, MO 63110 USA

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

[6] Virginia Polytech Inst & State Univ, Bradley Dept Elect & Comp Engn, Arlington, VA 22203 USA

[7] Washington Univ, Immunol Grad Program, Sch Med, St Louis, MO 63110 USA

[8] Washington Univ, Med Scientist Training Program, Sch Med, St Louis, MO 63110 USA

[9] Washington Univ Sch Med St Louis, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA

[10] Washington Univ Sch Med St Louis, Sch Med, Dept Neurol, St. Louis, MO 63110 USA

[11] Washington Univ Sch Med St Louis, Bursky Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63112 USA

[12] Washington Univ Sch Med St Louis, Sch Med, Dept Genet, St Louis, MO 63110 USA

来源：

IMMUNITY | 2024年 / 57卷 / 06期

基金：

美国国家卫生研究院;

关键词：

MONOCYTES; MYELINOGENESIS; MAINTENANCE; MACROPHAGES; CONTRIBUTE; VARIANTS; TURNOVER; DRIVES; CELLS; MODEL;

D O I：

10.1016/j.immuni.2024.05.005

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Recent single -cell RNA sequencing studies have revealed distinct microglial states in development and disease. These include proliferative -region -associated microglia (PAMs) in developing white matter and disease -associated microglia (DAMs) prevalent in various neurodegenerative conditions. PAMs and DAMs share a similar core gene signature. However, the extent of the dynamism and plasticity of these microglial states, as well as their functional significance, remains elusive, partly due to the lack of specific tools. Here, we generated an inducible Cre driver line, Clec7a-CreER T2 , that targets PAMs and DAMs in the brain parenchyma. Utilizing this tool, we profiled labeled cells during development and in several disease models, uncovering convergence and context -dependent differences in PAM and DAM gene expression. Through long-term tracking, we demonstrated microglial state plasticity. Lastly, we specifically depleted DAMs in demyelination, revealing their roles in disease recovery. Together, we provide a versatile genetic tool to characterize microglial states in CNS development and disease.

引用

页码：1394 / 1412.e8

页数：28

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