TY - JOUR
T1 - Mapping microglia states in the human brain through the integration of high-dimensional techniques
AU - Sankowski, Roman
AU - Böttcher, Chotima
AU - Masuda, Takahiro
AU - Geirsdottir, Laufey
AU - Sagar,
AU - Sindram, Elena
AU - Seredenina, Tamara
AU - Muhs, Andreas
AU - Scheiwe, Christian
AU - Shah, Mukesch Johannes
AU - Heiland, Dieter Henrik
AU - Schnell, Oliver
AU - Grün, Dominic
AU - Priller, Josef
AU - Prinz, Marco
N1 - Funding Information:
The authors thank J. Bodinek-Wersing, T. El Gaz, E. Barleon and A. Frömming for excellent technical support. R.S. is supported by the Berta-Ottenstein Programme for Clinician Scientists. M.P. is supported by the Sobek Foundation, the Ernst-Jung Foundation, the German Research Foundation (SFB 992, SFB1160, Reinhart-Koselleck-Grant) and the Ministry of Science, Research and Arts, Baden-Wuerttemberg (Sonderlinie “Neuroinflammation”) and by the BMBF-funded competence network of multiple sclerosis (KKNMS). This study was supported by the German Research Foundation (DFG) under Germany’s Excellence Strategy (CIBSS, EXC-2189, project ID 390939984). The authors would also like to acknowledge the assistance of the BCRT Flow Cytometry Lab (Charité—Universitätsmedizin Berlin, Germany). C.B., M.P. and J.P. are supported by the German Research Foundation (SFB/TRR167 “NeuroMac”). J.P. received additional funding from the Berlin Institute of Health (CRG2aSP6) and the UK DRI (Momentum Award). D.G. was supported by the Max Planck Society, the German Research Foundation (DFG) (SPP1937 GR4980/1-1, GR4980/3-1 and GRK2344 MeInBio), by the DFG under Germany’s Excellence Strategy (CIBSS, EXC-2189, project ID 390939984), by the ERC (818846, ImmuNiche, ERC-2018-COG) and by the Behrens-Weise-Foundation.
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Microglia are tissue-resident macrophages of the CNS that orchestrate local immune responses and contribute to several neurological and psychiatric diseases. Little is known about human microglia and how they orchestrate their highly plastic, context-specific adaptive responses during pathology. Here we combined two high-dimensional technologies, single-cell RNA-sequencing and time-of-flight mass cytometry, to identify microglia states in the human brain during homeostasis and disease. This approach enabled us to identify and characterize a previously unappreciated spectrum of transcriptional states in human microglia. These transcriptional states are determined by their spatial distribution, and they further change with aging and brain tumor pathology. This description of multiple microglia phenotypes in the human CNS may open promising new avenues for subset-specific therapeutic interventions.
AB - Microglia are tissue-resident macrophages of the CNS that orchestrate local immune responses and contribute to several neurological and psychiatric diseases. Little is known about human microglia and how they orchestrate their highly plastic, context-specific adaptive responses during pathology. Here we combined two high-dimensional technologies, single-cell RNA-sequencing and time-of-flight mass cytometry, to identify microglia states in the human brain during homeostasis and disease. This approach enabled us to identify and characterize a previously unappreciated spectrum of transcriptional states in human microglia. These transcriptional states are determined by their spatial distribution, and they further change with aging and brain tumor pathology. This description of multiple microglia phenotypes in the human CNS may open promising new avenues for subset-specific therapeutic interventions.
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U2 - 10.1038/s41593-019-0532-y
DO - 10.1038/s41593-019-0532-y
M3 - Article
C2 - 31740814
AN - SCOPUS:85072670087
SN - 1097-6256
VL - 22
SP - 2098
EP - 2110
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 12
ER -
