Identification of a Unique TGF-β Dependent Molecular and Functional Signature in Microglia

Microglia are myeloid cells of the central nervous system (CNS) that participate both in normal CNS function and disease. We investigated the molecular signature of microglia and identified 239 genes and 8 microRNAs that were uniquely or highly expressed in microglia vs. myeloid and other immune cells. Out of 239 genes, 106 were enriched in microglia as compared to 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. Based on this signature, we found a crucial role for TGF-β in microglial biology that included: 1) the requirement of TGF-β for the in vitro development of microglia that express the microglial molecular signature characteristic of adult microglia; and 2) the absence of microglia in CNS TGF-β1 deficient mice. Our results identify a unique microglial signature that is dependent on TGF-β signaling which provides insights into microglial biology and the possibility of targeting microglia for the treatment of CNS disease. miRNA/gene expression profiles of microglia during development and adult mice. MG400 custom-design Nanosting chips, miRNA chips and Afymetrix arrays were used to identify unique molecular microglia signature in microglia as compared to immune and neural cells. Total RNA was isolated from FACS sorted adult FCRLS+ microglia, neuroglial cells and immune cells. Total RNA was extracted using mirVanaTM miRNA isolation kit (Ambion) according to the manufacturer's protocol. nCounter Nansotring custom-made MG400 chip and nCounter Mouse miRNA Assay Kit were used for gene and miRNA expression profile.