Microglia development follows a stepwise program to regulate brain homeostasis

被引：843

作者：

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

Winter, Deborah R. ^{[1
]}

Giladi, Amir ^{[1
]}

Aguilar, Stephanie Vargas ^{[3
,4
,5
,6
]}

Spinrad, Amit ^{[1
,2
]}

Sarrazin, Sandrine ^{[3
,4
,5
]}

Ben-Yehuda, Hila ^{[2
]}

David, Eyal ^{[1
]}

Gonzalez, Fabiola Zelada ^{[3
,4
,5
]}

Perrin, Pierre ^{[3
,4
,5
]}

Keren-Shaul, Hadas ^{[1
]}

Gury, Meital ^{[1
]}

Lara-Astaiso, David ^{[1
]}

Thaiss, Christoph A. ^{[1
]}

Cohen, Merav ^{[2
]}

Halpern, Keren Bahar ^{[7
]}

Baruch, Kuti ^{[2
]}

Deczkowska, Aleksandra ^{[2
]}

Lorenzo-Vivas, Erika ^{[1
]}

Itzkovitz, Shalev ^{[7
]}

Elinav, Eran ^{[1
]}

Sieweke, Michael H. ^{[3
,4
,5
,6
]}

Schwartz, Michal ^{[2
]}

Amit, Ido ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Immunol, Rehovot, Israel

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

[3] Univ Aix Marseille, CIML, UM2, Campus Luminy, Marseille, France

[4] INSERM, U1104, Marseille, France

[5] CNRS, UMR7280, Marseille, France

[6] Helmholt Gemeinschaft MDC, Max Delbruck Ctr Mol Med, Robert Rossle Str 10, D-13125 Berlin, Germany

[7] Weizmann Inst Sci, Dept Cell Biol, Rehovot, Israel

来源：

SCIENCE | 2016年 / 353卷 / 6301期

基金：

欧洲研究理事会;

关键词：

TISSUE-RESIDENT MACROPHAGES; HEMATOPOIETIC STEM-CELLS; HUMAN GENOME; MYELOID PROGENITORS; IMMUNE INVOLVEMENT; LANGERHANS CELLS; GENE-EXPRESSION; CHOROID-PLEXUS; SELF-RENEWAL; ADULT LIFE;

D O I：

10.1126/science.aad8670

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Microglia, the resident myeloid cells of the central nervous system, play important roles in life-long brain maintenance and in pathology. Despite their importance, their regulatory dynamics during brain development have not been fully elucidated. Using genome-wide chromatin and expression profiling coupled with single-cell transcriptomic analysis throughout development, we found that microglia undergo three temporal stages of development in synchrony with the brain-early, pre-, and adult microglia-which are under distinct regulatory circuits. Knockout of the gene encoding the adult microglia transcription factor MAFB and environmental perturbations, such as those affecting the microbiome or prenatal immune activation, led to disruption of developmental genes and immune response pathways. Together, our work identifies a stepwise microglia developmental program integrating immune response pathways that may be associated with several neurodevelopmental disorders.

引用

页数：12

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