For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
147
views
33
references
 Top references
cited by
568
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      217
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

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

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references33

          • Record: found
          • Abstract: found
          • Article: not found

          Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.

          M Shull, I Ormsby, A Kier … (1992)
          Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional growth factor that has profound regulatory effects on many developmental and physiological processes. Disruption of the TGF-beta 1 gene by homologous recombination in murine embryonic stem cells enables mice to be generated that carry the disrupted allele. Animals homozygous for the mutated TGF-beta 1 allele show no gross developmental abnormalities, but about 20 days after birth they succumb to a wasting syndrome accompanied by a multifocal, mixed inflammatory cell response and tissue necrosis, leading to organ failure and death. TGF-beta 1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.
          Article 0 comments Cited 483 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The P2Y12 receptor regulates microglial activation by extracellular nucleotides.

            Sharon E Haynes, Gunther Hollopeter, Guang Yang … (2006)
            Microglia are primary immune sentinels of the CNS. Following injury, these cells migrate or extend processes toward sites of tissue damage. CNS injury is accompanied by release of nucleotides, serving as signals for microglial activation or chemotaxis. Microglia express several purinoceptors, including a G(i)-coupled subtype that has been implicated in ATP- and ADP-mediated migration in vitro. Here we show that microglia from mice lacking G(i)-coupled P2Y(12) receptors exhibit normal baseline motility but are unable to polarize, migrate or extend processes toward nucleotides in vitro or in vivo. Microglia in P2ry(12)(-/-) mice show significantly diminished directional branch extension toward sites of cortical damage in the living mouse. Moreover, P2Y(12) expression is robust in the 'resting' state, but dramatically reduced after microglial activation. These results imply that P2Y(12) is a primary site at which nucleotides act to induce microglial chemotaxis at early stages of the response to local CNS injury.
            Article 0 comments Cited 479 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool.

              Bahareh Ajami, Jami Bennett, Charles Krieger … (2011)
              In multiple sclerosis and the experimental autoimmune encephalitis (EAE) mouse model, two pools of morphologically indistinguishable phagocytic cells, microglia and inflammatory macrophages, accrue from proliferating resident precursors and recruitment of blood-borne progenitors, respectively. Whether these cell types are functionally equivalent is hotly debated, but is challenging to address experimentally. Using a combination of parabiosis and myeloablation to replace circulating progenitors without affecting CNS-resident microglia, we found a strong correlation between monocyte infiltration and progression to the paralytic stage of EAE. Inhibition of chemokine receptor-dependent recruitment of monocytes to the CNS blocked EAE progression, suggesting that these infiltrating cells are essential for pathogenesis. Finally, we found that, although microglia can enter the cell cycle and return to quiescence following remission, recruited monocytes vanish, and therefore do not ultimately contribute to the resident microglial pool. In conclusion, we identified two distinct subsets of myelomonocytic cells with distinct roles in neuroinflammation and disease progression.
              Article 0 comments Cited 423 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-journal-id): 9809671
                Journal ID (pubmed-jr-id): 21092
                Journal ID (nlm-ta): Nat Neurosci
                Journal ID (iso-abbrev): Nat. Neurosci.
                Title: Nature neuroscience
                ISSN (Print): 1097-6256
                ISSN (Electronic): 1546-1726
                Publication date Nihms-submitted: 17 May 2014
                Publication date (Electronic): 08 December 2013
                Publication date (Print): January 2014
                Publication date PMC-release: 01 July 2014
                Volume: 17
                Issue: 1
                Pages: 131-143
                Affiliations
                [1 ]Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02112
                [2 ]Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
                [3 ]Neuroimmunology Unit, Montréal Neurological Institute, McGill University, Montréal, Québec, Canada
                [4 ]Brain Science Institute and Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA
                [5 ]Department of Immunology, Cleveland Clinic, Cleveland, Ohio, USA
                Author notes
                [* ]Corresponding authors: Oleg Butovsky, Center for Neurologic Diseases, Brigham and Women’s Hospital, 77 Avenue Louis Pasteur HIM 730, Boston, MA 02115, Tel: +1-617-525-5300, Fax: +1-617-525-5252, obutovsky@ 123456rics.bwh.harvard.edu or Howard L. Weiner, Center for Neurologic Diseases, Brigham and Women’s Hospital, 77 Avenue Louis Pasteur HIM 730, Boston, MA 02115, Tel: +1-617-525-5300, Fax: +1-617-525-5252, hweiner@ 123456rics.bwh.harvard.edu
                Article
                Manuscript ID: NIHMS560033
                DOI: 10.1038/nn.3599
                PMC ID: 4066672
                PubMed ID: 24316888
                SO-VID: ab303d76-78eb-4c83-98db-663ef7318d27
                History
                Categories
                Subject: Article

                ScienceOpen disciplines: Neurosciences
                Data availability:
                ScienceOpen disciplines: Neurosciences

                Comments

                Comment on this article

                scite_

                Similar content217

                See all similar

                Cited by1,048

                See all cited by

                Most referenced authors1,669

                See all reference authors