{"doi":"10.1101/2022.01.10.475705","title":"Single-nucleus RNA-seq of normal-appearing brain regions in relapsing-remitting vs. secondary progressive multiple sclerosis","abstract":"Summary Multiple sclerosis (MS) is an immune-mediated demyelinating disease that alters central nervous system (CNS) functions. Relapsing-remitting MS (RRMS) is the most common form, which can transform into secondary-progressive MS (SPMS) that is associated with progressive neurodegeneration. Single-nucleus RNA sequencing (snRNA-seq) of MS lesions identified disease-related transcriptomic alterations; however, their relationship to non-lesioned MS brain regions has not been reported and which could identify prodromal or other disease susceptibility signatures. Here, snRNA-seq was used to generate high-quality RRMS vs. SPMS datasets of 33,197 nuclei from 8 normal-appearing MS brains, which revealed divergent cell type-specific changes. Notably, SPMS brains downregulated astrocytic sphingosine kinases ( SPHK1/2 ) – the enzymes required to phosphorylate and activate the MS drug, fingolimod. This reduction was modeled with astrocyte-specific Sphk1/2 null mice in which fingolimod lost activity, supporting functionality of observed transcriptomic changes. These data provide an initial resource for studies of single cells from non-lesioned RRMS and SPMS brains.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":302509,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9454,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":889638,"name":"Yunjiao Zhu","orcid":"0000-0003-3730-3374","position":1,"is_corresponding":false},{"id":772320,"name":"Deepa Jonnalagadda","orcid":"0000-0002-1511-8197","position":2,"is_corresponding":false},{"id":38361,"name":"William J. Romanow","orcid":"0000-0002-3808-6482","position":3,"is_corresponding":false},{"id":38354,"name":"Carter R. Palmer","orcid":"0000-0002-2385-2068","position":4,"is_corresponding":false},{"id":889639,"name":"Benjamin Siddoway","orcid":"0000-0002-3430-4892","position":5,"is_corresponding":false},{"id":772321,"name":"Richard Rivera","orcid":"0000-0001-6138-3306","position":6,"is_corresponding":false},{"id":109686,"name":"Ranjan Dutta","orcid":"0000-0001-8502-4455","position":7,"is_corresponding":false},{"id":231866,"name":"Bruce D. Trapp","orcid":"0000-0001-6682-3737","position":8,"is_corresponding":false},{"id":38374,"name":"Jerold Chun","orcid":"0000-0003-3964-0921","position":9,"is_corresponding":false},{"id":584518,"name":"Yasuyuki Kihara","orcid":"0000-0001-7462-3006","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:16.279991Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}