title: Uncovering MicroRNA Regulatory Hubs that Modulate Plasma Cell Differentiation.
abstract: Using genome-wide approaches, we studied the microRNA (miRNA) expression profile during human plasma cell (PC) differentiation induced by stimulation of human blood B cells with T follicular helper cell-dependent signals. Combining the profiles of differentially expressed genes in PC differentiation with gene ontology (GO) analysis revealed that a significant group of genes involved in the transcription factor (TF) activity was preferentially changed. We thus focused on studying the effects of differentially expressed miRNAs on several key TFs in PC differentiation. Cohorts of differentially expressed miRNAs cooperating as miRNA hubs were predicted and validated to modulate key TFs, including a down-regulated miRNA hub containing miR-101-3p, -125b-5p, and -223-3p contributing to induction of PRDM1 as well as an up-regulated miRNA hub containing miR-34a-5p, -148a-3p, and -183-5p suppressing BCL6, BACH2, and FOXP1. Induced expression of NF-κB and PRDM1 during PC differentiation controlled the expression of up- and down-regulated miRNA hubs, respectively. Co-expression of miR-101-3p, -125b-5p, and -223-3p in stimulated B cells showed synergistic effects on inhibition of PC formation, which can be rescued by re-introduction of PRDM1. Together, we catalogue the complex roadmap of miRNAs and their functional interplay in collaboratively directing PC differentiation.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.|Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Tsai
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.|Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Kuo-Hsuan
authors.initials: KH
authors.lastname: Hung
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: I-Ying
authors.initials: IY
authors.lastname: Lin
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Shin-Tang
authors.initials: ST
authors.lastname: Su
authors.affiliation: Institute of Information Science, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Shih-Ying
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Chung
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.|Biodiversity Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Tong-Cheng
authors.initials: TC
authors.lastname: Wang
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.|Biodiversity Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Wen-Hsiung
authors.initials: WH
authors.lastname: Li
authors.affiliation: Institute of Information Science, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Arthur Chun-Chieh
authors.initials: AC
authors.lastname: Shih
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.|Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Kuo-I
authors.initials: KI
authors.lastname: Lin
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D064368:Healthy Volunteers; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D005810:Multigene Family; D016328:NF-kappa B / Q000378:metabolism; D010950:Plasma Cells / Q000166:cytology* / Q000378:metabolism*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D012097:Repressor Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1