A single-cell compendium of human cerebrospinal fluid identifies disease-associated immune cell populations
Claudia Cantoni, … , Brian T. Edelson, Gregory F. Wu
Claudia Cantoni, … , Brian T. Edelson, Gregory F. Wu
Published January 2, 2025
Citation Information: J Clin Invest. 2025;135(1):e177793. https://doi.org/10.1172/JCI177793.
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A single-cell compendium of human cerebrospinal fluid identifies disease-associated immune cell populations

Abstract

Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimer’s disease, Parkinson’s disease, COVID-19, and autoimmune encephalitis, were included. We found differences in lymphocyte and myeloid subset frequencies across different diseases as well as in their distribution between blood and CSF. We identified what we believe to be a new subset of AREG+ dendritic cells exclusive to the CSF that was more abundant in subjects with MS compared with healthy controls. Finally, transcriptional cell states in CSF microglia-like cells and lymphoid subsets were elucidated. Altogether, we have created a reference compendium for single-cell transcriptional profiling encompassing CSF immune cells useful to the scientific community for future studies on neurologic diseases.

Authors

Claudia Cantoni, Roman A. Smirnov, Maria Firulyova, Prabhakar S. Andhey, Tara R. Bradstreet, Ekaterina Esaulova, Marina Terekhova, Elizabeth A. Schwarzkopf, Nada M. Abdalla, Maksim Kleverov, Joseph J. Sabatino Jr., Kang Liu, Nicholas Schwab, Gerd Meyer zu Hörste, Anne H. Cross, Maxim N. Artyomov, Brian T. Edelson, Gregory F. Wu

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Figure 5

Cell type diversity and statistical comparison of B cells and plasmablasts in PBMCs and CSF between 5 main disease groups.

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Cell type diversity and statistical comparison of B cells and plasmablas...
(A) Overall UMAP of B cells in both tissues combined. (B and C) UMAP of B cells and plasmablasts in PBMCs (B) and CSF (C) colored by the main clusters. (D) Selection of marker genes represented by dot plot for each respective cluster of B cells and plasmablasts. (E) Percentage of major clusters of B cells and plasmablasts in both PBMCs and CSF. (F) Cell proportions in CSF B cell and plasmablast populations across 5 disease groups. (G) UMAP of plasmablast subcluster in both tissues combined. (H and I) UMAP of plasmablast subcluster in PBMCs (H) and CSF (I). (J) Selection of marker genes represented by dot plot for each plasmablast subcluster. (K) Comparison of plasmablast subcluster percentages between PBMCs and CSF. (L) Cell proportions of each CSF plasmablast subcluster across 5 disease groups. In E and K, the test of pairwise comparisons of cell type percentages in PBMCs and CSF was determined by post hoc Dunn’s test with Benjamini-Hochberg adjustment. In F and L, significance for pairwise comparisons between HC and all other disease groups was determined by post hoc Dunn’s test with Benjamini-Hochberg adjustment. *Padj < 0.05, **Padj < 0.01, ****Padj < 0.0001.