To investigate the transcriptional profile of macrophages in central nervous system (CNS) in patients with multiple sclerosis (MS).

Brain macrophages consist of microglia and central nervous system (CNS) border-associated macrophages (CAMs), and CAMs are transcriptionally distinct from microglia. However, the transcriptional profile in a pathologic state in humans such as MS remains to be elucidated.

We analyzed raw single-cell RNA sequencing (scRNA-seq) data of brain cells with patients with MS obtained from the previous studies (Lake et al, 2018; Jakel et al, 2019; Schirmer et al, 2019). The expression level of transcripts was used for cell clustering, and brain macrophages were identified. The genes differentially expressed in each subcluster of brain macrophages were assessed.

The scRNA-seq data from 110,121 CNS cells (including 45,573 cells from MS patients) were analyzed. After cell clustering, 2,821 cells (including 2,247 cells from MS patients) had transcriptional profiles suggestive of macrophages and were distinct from other clusters such as microglia or oligodendrocytes. We found 8 genes were upregulated (with log2 fold change >1) in brain macrophages in MS patients compared to healthy controls. The cells in the macrophage cluster were further classified into subclusters, with each cluster having different expression profiles.

CAMs might increase in number and be transcriptionally heterogenous in patients with MS.