Single cell transcriptomics of cerebrospinal fluid cells from patients with recent-onset narcolepsy

Narcolepsy is a rare cause of excessive daytime sleepiness and may be associated or not with cataplexy, i.e. sudden muscle weakness. These forms are designated NAR-type 1 (NT1) and -type 2 (NT2), respectively. Notable characteristics of narcolepsy are that most patients carry the HLA-DQB1*06:02 allele and NT1-patients have highly decreased levels hypocretin-1 (synonym orexin-A) in the cerebrospinal fluid (CSF). The pathogenesis of narcolepsy is still enigmatic but the strung HLA-bias and increased frequencies of CD4+ T cells reactive to hypocretin in the peripheral blood suggest autoimmune processes in the hypothalamus. Here we analyzed the transcriptomes of single CSF-cells from 16 narcoleptic patients by mRNAseq. As controls, we used single cells from patients with multiple sclerosis, radiologically isolated syndrome, and idiopathic intracranial hypertension. We identified 20 clusters of different cell types and >1000 genes that were differentially regulated between the different diseases. Surprisingly, the strongest upregulation in narcolepsy patients as compared to controls were the genome-encoded MTRNR2L12 and MTRNR2L8 peptides, which are homologous to mitochondria-encoded HUMANIN peptide that is known playing a role in other neurological diseases. We analyzed the transcriptome of single cells isolated from cerebrospinal fluid (CSF) from patients with NT1 and NT2 with recent disease onset. As controls, we used CSF cells from patients with multiple sclerosis (MS) and radiologically isolated syndrome (RIS) and idiopathic intracranial hypertension (IIH), i.e. from patients with a chronic inflammatory and a non-inflammatory neurological disease, respectively. Author statement: Fastq raw data files from patients are not uploaded due to data protection concerns. ADT barcode sequence TotalSeq™-C0072 anti-human CD4 Antibody TGTTCCCGCTCAACT TotalSeq™-C0046 anti-human CD8 Antibody GCGCAACTTGATGAT ---------------------------- Submitters state "Due to data protection concerns, our institution does not permit the upload of raw sequencing files generated from human samples.