RT Journal Article
SR Electronic
T1 Single-cell RNA-seq analysis of human CSF microglia and myeloid cells in neuroinflammation
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e732
DO 10.1212/NXI.0000000000000732
VO 7
IS 4
A1 Esaulova, Ekaterina
A1 Cantoni, Claudia
A1 Shchukina, Irina
A1 Zaitsev, Konstantin
A1 Bucelli, Robert C.
A1 Wu, Gregory F.
A1 Artyomov, Maxim N.
A1 Cross, Anne H.
A1 Edelson, Brian T.
YR 2020
UL http://nn.neurology.org/content/7/4/e732.abstract
AB Objective To identify and characterize myeloid cell populations within the CSF of patients with MS and anti-myelin oligodendrocyte glycoprotein (MOG) disorder by high-resolution single-cell gene expression analysis.Methods Single-cell RNA sequencing (scRNA-seq) was used to profile individual cells of CSF and blood from 2 subjects with relapsing-remitting MS (RRMS) and one with anti-MOG disorder. Publicly available scRNA-seq data from the blood and CSF of 2 subjects with HIV were also analyzed. An informatics pipeline was used to cluster cell populations by transcriptomic profiling. Based on gene expression by CSF myeloid cells, a flow cytometry panel was devised to examine myeloid cell populations from the CSF of 11 additional subjects, including individuals with RRMS, anti-MOG disorder, and control subjects without inflammatory demyelination.Results Common myeloid populations were identified within the CSF of subjects with RRMS, anti-MOG disorder, and HIV. These included monocytes, conventional and plasmacytoid dendritic cells, and cells with a transcriptomic signature matching microglia. Microglia could be discriminated from other myeloid cell populations in the CSF by flow cytometry.Conclusions High-resolution single-cell gene expression analysis clearly distinguishes distinct myeloid cell types present within the CSF of subjects with neuroinflammation. A population of microglia exists within the human CSF, which is detectable by surface protein expression. The function of these cells during immunity and disease requires further investigation.AD=Alzheimer disease; ALS=amyotrophic lateral sclerosis; BAM=border-associated macrophage; CCA=canonical correlation analysis; cDC=conventional DC; DAM=disease-associated microglia; DC=dendritic cell; HC=healthy control; HLA-DR=human leukocyte antigen DR; IIH=idiopathic intracranial hypertension; MOG=myelin oligodendrocyte glycoprotein; NMO=neuromyelitis optica; PBMC=peripheral blood mononuclear cell; PCA=principal component analysis; pDC=plasmacytoid DC; RRMS=relapsing-remitting MS; scRNA-seq=single-cell RNA sequencing; UMAP=Uniform Manifold Approximation and Projection