Journal Article DZNE-2020-01365

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Novel Hexb-based tools for studying microglia in the CNS.

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2020
Springer Nature Limited London

Nature immunology 21(7), 802 - 815 () [10.1038/s41590-020-0707-4]

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Abstract: Microglia and central nervous system (CNS)-associated macrophages (CAMs), such as perivascular and meningeal macrophages, are implicated in virtually all diseases of the CNS. However, little is known about their cell-type-specific roles in the absence of suitable tools that would allow for functional discrimination between the ontogenetically closely related microglia and CAMs. To develop a new microglia gene targeting model, we first applied massively parallel single-cell analyses to compare microglia and CAM signatures during homeostasis and disease and identified hexosaminidase subunit beta (Hexb) as a stably expressed microglia core gene, whereas other microglia core genes were substantially downregulated during pathologies. Next, we generated HexbtdTomato mice to stably monitor microglia behavior in vivo. Finally, the Hexb locus was employed for tamoxifen-inducible Cre-mediated gene manipulation in microglia and for fate mapping of microglia but not CAMs. In sum, we provide valuable new genetic tools to specifically study microglia functions in the CNS.

Keyword(s): Animals (MeSH) ; Brain: cytology (MeSH) ; Brain: immunology (MeSH) ; Brain: pathology (MeSH) ; CRISPR-Cas Systems: genetics (MeSH) ; Encephalomyelitis, Autoimmune, Experimental: immunology (MeSH) ; Encephalomyelitis, Autoimmune, Experimental: pathology (MeSH) ; Facial Nerve Injuries: immunology (MeSH) ; Facial Nerve Injuries: pathology (MeSH) ; Gene Knock-In Techniques (MeSH) ; Genes, Reporter: genetics (MeSH) ; Genetic Loci: genetics (MeSH) ; Humans (MeSH) ; Intravital Microscopy (MeSH) ; Luminescent Agents: chemistry (MeSH) ; Luminescent Proteins: chemistry (MeSH) ; Luminescent Proteins: genetics (MeSH) ; Macrophages: immunology (MeSH) ; Macrophages: metabolism (MeSH) ; Mice (MeSH) ; Microglia: immunology (MeSH) ; Microglia: metabolism (MeSH) ; NIH 3T3 Cells (MeSH) ; RNA-Seq (MeSH) ; Single-Cell Analysis (MeSH) ; Transfection (MeSH) ; beta-Hexosaminidase beta Chain: genetics (MeSH) ; beta-Hexosaminidase beta Chain: metabolism (MeSH) ; Luminescent Agents ; Luminescent Proteins ; red fluorescent protein ; beta-Hexosaminidase beta Chain

Classification:

Contributing Institute(s):
  1. Translational Neuropsychiatry (AG Priller)
Research Program(s):
  1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2020
Database coverage:
Medline ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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Institute Collections > B DZNE > B DZNE-AG Priller
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Author Correction: Novel Hexb-based tools for studying microglia in the CNS
Nature immunology 21(10), 1302 () [10.1038/s41590-020-0774-6]  Download fulltext Files BibTeX | EndNote: XML, Text | RIS


 Record created 2020-11-23, last modified 2024-03-21


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