TY - JOUR
T1 - Novel Hexb-based tools for studying microglia in the CNS
AU - Masuda, Takahiro
AU - Amann, Lukas
AU - Sankowski, Roman
AU - Staszewski, Ori
AU - Lenz, Maximilian
AU - d´Errico, Paolo
AU - Snaidero, Nicolas
AU - Costa Jordão, Marta Joana
AU - Böttcher, Chotima
AU - Kierdorf, Katrin
AU - Jung, Steffen
AU - Priller, Josef
AU - Misgeld, Thomas
AU - Vlachos, Andreas
AU - Luehmann, Melanie Meyer
AU - Knobeloch, Klaus Peter
AU - Prinz, Marco
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85086761190&partnerID=8YFLogxK
U2 - 10.1038/s41590-020-0707-4
DO - 10.1038/s41590-020-0707-4
M3 - Article
C2 - 32541832
AN - SCOPUS:85086761190
SN - 1529-2908
VL - 21
SP - 802
EP - 815
JO - Nature Immunology
JF - Nature Immunology
IS - 7
ER -