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

Oleg Butovsky, Mark P. Jedrychowski, Craig S. Moore, Ron Cialic, Amanda J. Lanser, Galina Gabriely, Thomas Koeglsperger, Ben Dake, Pauline M. Wu, Camille E. Doykan, Zain Fanek, Liping Liu, Zhuoxun Chen, Jeffrey D. Rothstein, Richard M. Ransohoff, Steven P. Gygi, Jack P. Antel, Howard L. Weiner

Research output: Contribution to journalArticle

Abstract

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-β 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-β1-deficient mice. Our results identify a unique microglial signature that is dependent on TGF-β signaling and provide insights into microglial biology and the possibility of targeting microglia for the treatment of CNS disease.

Original languageEnglish (US)
Pages (from-to)131-143
Number of pages13
JournalNature neuroscience
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2014

ASJC Scopus subject areas

  • Neuroscience(all)

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    Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., Fanek, Z., Liu, L., Chen, Z., Rothstein, J. D., Ransohoff, R. M., Gygi, S. P., Antel, J. P., & Weiner, H. L. (2014). Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nature neuroscience, 17(1), 131-143. https://doi.org/10.1038/nn.3599