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

Nat Neurosci. 2014 Jan;17(1):131-43. doi: 10.1038/nn.3599. Epub 2013 Dec 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Antigens, CD / metabolism
  • Cells, Cultured
  • Central Nervous System / cytology*
  • Chromatography, Ion Exchange
  • Embryo, Mammalian
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Developmental / physiology
  • Humans
  • Male
  • Mass Spectrometry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / genetics
  • Microglia / classification
  • Microglia / metabolism*
  • Neurons / metabolism
  • Receptors, Purinergic P2Y12 / metabolism
  • Signal Transduction / genetics*
  • Tissue Array Analysis
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*


  • Antigens, CD
  • MicroRNAs
  • P2ry12 protein, rat
  • Receptors, Purinergic P2Y12
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1

Associated data

  • GEO/GSE48579