TY - JOUR
T1 - Peripheral nerve resident macrophages share tissue-specific programming and features of activated microglia
AU - Wang, Peter L.
AU - Yim, Aldrin K.Y.
AU - Kim, Ki Wook
AU - Avey, Denis
AU - Czepielewski, Rafael S.
AU - Colonna, Marco
AU - Milbrandt, Jeffrey
AU - Randolph, Gwendalyn J.
N1 - Funding Information:
We thank all our collaborators at Washington University School of Medicine (WUSM) for their advice and discussion. We thank Richard Head, Ruteja Barve, and the Genome Technology Access Center (GTAC) at WUSM for discussion and assistance with RNA sequencing. We thank John Baer and David DeNardo for providing Flt3-Cre LSL-YFPfl/fl mice. We thank Kory Lavine for providing Ccr2GFP/GFP mice and Marco Colonna and Susan Gilfillan for providing IL-34LacZ/LacZ mice. We thank Jesse Williams, Amy Strickland, and Yingyue Zhou for experimental assistance. We thank Wilbur Song for discussion and Joseph Bloom for reading the manuscript. We also thank our colleagues at the ImmGen Project consortium, including Christophe Benoist PI of the Immgen Project), fellow scientists who submitted samples, and Kumba Seddu for coordinating transfer of samples and data. We thank Nan Zhang for help with revisions and Emma Erlich for help with data analysis. This project was supported by NIH grants R37AI049653 and DP1DK109668 to G.J.R., RF1AG013730 and R01NS105645 to J.M., and the Principles in Pulmonary Research training grant (T32 HL007317-41) to P.L.W. Further support was provided by P30AR073752 that supports Rheumatic Diseases Research Resource-Based Center and NIH R24 AI072073 that funds the ImmGen Project.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Whereas microglia are recognized as fundamental players in central nervous system (CNS) development and function, much less is known about macrophages of the peripheral nervous system (PNS). Here, by comparing gene expression across neural and conventional tissue-resident macrophages, we identified transcripts that were shared among neural resident macrophages as well as selectively enriched in PNS macrophages. Remarkably, PNS macrophages constitutively expressed genes previously identified to be upregulated by activated microglia during aging, neurodegeneration, or loss of Sall1. Several microglial activation-associated and PNS macrophage-enriched genes were also expressed in spinal cord microglia at steady state. We further show that PNS macrophages rely on IL-34 for maintenance and arise from both embryonic and hematopoietic precursors, while their expression of activation-associated genes did not differ by ontogeny. Collectively, these data uncover shared and unique features between neural resident macrophages and emphasize the role of nerve environment for shaping PNS macrophage identity.
AB - Whereas microglia are recognized as fundamental players in central nervous system (CNS) development and function, much less is known about macrophages of the peripheral nervous system (PNS). Here, by comparing gene expression across neural and conventional tissue-resident macrophages, we identified transcripts that were shared among neural resident macrophages as well as selectively enriched in PNS macrophages. Remarkably, PNS macrophages constitutively expressed genes previously identified to be upregulated by activated microglia during aging, neurodegeneration, or loss of Sall1. Several microglial activation-associated and PNS macrophage-enriched genes were also expressed in spinal cord microglia at steady state. We further show that PNS macrophages rely on IL-34 for maintenance and arise from both embryonic and hematopoietic precursors, while their expression of activation-associated genes did not differ by ontogeny. Collectively, these data uncover shared and unique features between neural resident macrophages and emphasize the role of nerve environment for shaping PNS macrophage identity.
UR - http://www.scopus.com/inward/record.url?scp=85085157949&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-16355-w
DO - 10.1038/s41467-020-16355-w
M3 - Article
C2 - 32439942
AN - SCOPUS:85085157949
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2552
ER -