Identification of a unique TGF-β dependent molecular and functional signature in microglia

被引：1857

作者：

Butovsky, Oleg ^{[1
]}

Jedrychowski, Mark P. ^{[2
]}

Moore, Craig S. ^{[3
]}

Cialic, Ron ^{[1
]}

Lanser, Amanda J. ^{[1
]}

Gabriely, Galina ^{[1
]}

Koeglsperger, Thomas ^{[1
]}

Dake, Ben ^{[1
]}

Wu, Pauline M. ^{[1
]}

Doykan, Camille E. ^{[1
]}

Fanek, Zain ^{[1
]}

Liu, LiPing ^{[4
]}

Chen, Zhuoxun ^{[5
,6
]}

Rothstein, Jeffrey D. ^{[5
,6
]}

Ransohoffl, Richard M. ^{[4
]}

Gygi, Steven P. ^{[2
]}

Antel, Jack P. ^{[3
]}

Weiner, Howard L. ^{[1
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Dept Neurol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[3] McGill Univ, Montreal Neurol Inst, Neuroimmunol Unit, Montreal, PQ, Canada

[4] Cleveland Clin, Dept Immunol, Cleveland, OH 44106 USA

[5] Johns Hopkins Univ, Brain Sci Inst, Baltimore, MD USA

[6] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA

来源：

NATURE NEUROSCIENCE | 2014年 / 17卷 / 01期

关键词：

GROWTH-FACTOR-BETA; EPIDERMAL LANGERHANS CELLS; MYELOID CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; TISSUE MACROPHAGES; BRAIN-DEVELOPMENT; ADULT MICROGLIA; NERVOUS-SYSTEM; MOUSE-BRAIN; STEM-CELLS;

D O I：

10.1038/nn.3599

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Microglia are myeloid cells of the CNS that participate both in normal CNS function and in disease. We investigated the molecular signature of microglia and identified 239 genes and 8 microRNAs that were uniquely or highly expressed in microglia versus myeloid and other immune cells. Of the 239 genes, 106 were enriched in microglia as compared with astrocytes, oligodendrocytes and neurons. This microglia signature was not observed in microglial lines or in monocytes recruited to the CNS, and was also observed in human microglia. We found that TGF-beta was required for the in vitro development of microglia that express the microglial molecular signature characteristic of adult microglia and that microglia were absent in the CNS of TGF-beta 1 deficient mice. Our results identify a unique microglial signature that is dependent on TGF-beta signaling and provide insights into microglial biology and the possibility of targeting microglia for the treatment of CNS disease.

引用

页码：131 / 143

页数：13

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