Identification of a Unique TGF-β Dependent Molecular and Functional Signature in Microglia
By O. Butovsky, Mark P. Jedrychowski, C. Moore, R. Cialic, Amanda J Lanser, Galina Gabriely, Thomas Koeglsperger, Ben Dake, Pauline M. Wu, Camille E. Doykan and 8 more. Nature Neuroscience, 2013
2,301 citations recorded by the source corpus.
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.
Subfields: Immunology, Neurology
View Paper: https://www.semanticscholar.org/paper/52486c83a41de8949de6905ae15a994d75388a8b
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Immunology
In Neurology
Citations in the corpus
- Microglia in Alzheimer’s disease (2018, background): “SORL1 Receptor for vesicular sorting of lipoproteins and various receptors Binds Aβ and directs it to lysosome (Caglayan et al., 2014).”
- Microglia states and nomenclature: A field at its crossroads (2022, neutral): “156 An associated term is ‘‘M0’’ microglia, which describes their state when cultured in the presence of transforming growth factor b (TGF b ) and CSF1 to mimic in vivo counter-parts.”
- TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques (2016, background): “However, phenotypic markers of migroglia, such as low expression of CD45 and high expression of the P2Y(12) receptor, are altered upon microglial activation and therefore do not precisely discriminate microglia from monocytes (Butovsky et al., 2014).”
- Differential roles of microglia and monocytes in the inflamed central nervous system (2014, background): “…initiate demyelination at EAE onset, as MDMs were the overwhelmingly dominant genes included a large spectrum of intracellular signaling components from the MAP-kinase pathways, as well as TGF and receptor, both of which are implicated in the naïve microglial phenotype (Butovsky et al., 2014).”
- Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution (2017, result): “Comparison with the set of 86 microglia signature genes defined by Butovsky et al. (2014), showed that microglial marker genes (including Csf1r, Tmem119, P2ry12, Hexb, and Sall1) were expressed at a relatively uniform level in the large majority of cells.”
- Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023, neutral): “When primary microglia are cultured with CSF1 and TGFβ, a significant increase in the expression of microglial signature genes is observed compared to CSF1 alone.(71)”
- Macrophages: development and tissue specialization. (2015, background): “Classical airway alveolar macrophages interact with alveolar epithelial cells through CD200 and TGF-β signaling, which ensures their noninflammatory state (134, 140).”
- Cell type– and brain region–resolved mouse brain proteome (2015, neutral): “Q4 8,409 7 (614) 7 (42) 6 (10) 9 (3) 400 144 34 Q3 Q2 Q1 Percent (n) cell specific Oligodendrocytes Cortical neurons”
- iPSC-derived human microglia-like cells to study neurological diseases (2017, neutral): “PC2 (15.4% var) reflects trajectory to Blood DCs. PC3 (7.6% var) reflects trajectory to monocytes (B) Heatmap and biclustering (Euclidean-distance) on 300 microglia, myeloid, and other immune related genes (Butovsky et al., 2014, Hickman et al., 2013, Zhang et al., 2014).”
- Tissue-Resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment (2014, background): “Finally, TGF-b was shown to regulate a microglia expression program through Smad TFs (Abutbul et al., 2012; Butovsky et al., 2014).”