title: Long Noncoding RNA Expression during Human B-Cell Development.
abstract: Long noncoding RNAs (lncRNAs) have emerged as important regulators of diverse cellular processes, but their roles in the developing immune system are poorly understood. In this study, we analysed lncRNA expression during human B-cell development by array-based expression profiling of eleven distinct flow-sorted B-cell subsets, comprising pre-B1, pre-B2, immature, naive, memory, and plasma cells from bone marrow biopsies (n = 7), and naive, centroblast, centrocyte, memory, and plasmablast cells from tonsil tissue samples (n = 6), respectively. A remapping strategy was used to assign the array probes to 37630 gene-level probe sets, reflecting recent updates in genomic and transcriptomic databases, which enabled expression profiling of 19579 long noncoding RNAs, comprising 3947 antisense RNAs, 5277 lincRNAs, 7625 pseudogenes, and 2730 additional lncRNAs. As a first step towards inferring the functions of the identified lncRNAs in developing B-cells, we analysed their co-expression with well-characterized protein-coding genes, a method known as "guilt by association". By using weighted gene co-expression network analysis, we identified 272 lincRNAs, 471 antisense RNAs, 376 pseudogene RNAs, and 64 lncRNAs within seven sub-networks associated with distinct stages of B-cell development, such as early B-cell development, B-cell proliferation, affinity maturation of antibody, and terminal differentiation. These data provide an important resource for future studies on the functions of lncRNAs in development of the adaptive immune response, and the pathogenesis of B-cell malignancies that originate from distinct B-cell subpopulations.
authors.affiliation: Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark; Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Petri
authors.affiliation: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Dybkær
authors.affiliation: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Bøgsted
authors.affiliation: Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark; Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Charlotte Albæk
authors.initials: CA
authors.lastname: Thrue
authors.affiliation: Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark; Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hagedorn
authors.affiliation: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmitz
authors.affiliation: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Julie Støve
authors.initials: JS
authors.lastname: Bødker
authors.affiliation: Department of Haematology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Johnsen
authors.affiliation: Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark; Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Sakari
authors.initials: S
authors.lastname: Kauppinen
mesh_terms: D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D016000:Cluster Analysis; D020869:Gene Expression Profiling / Q000379:methods*; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D014066:Palatine Tonsil / Q000166:cytology / Q000378:metabolism; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: D062085:RNA, Long Noncoding