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Uncovering MicroRNA Regulatory Hubs that Modulate Plasma Cell Differentiation
- Source :
- Scientific Reports
- Publication Year :
- 2015
-
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.
- Subjects :
- Cellular differentiation
Plasma Cells
Biology
Bioinformatics
Article
Transcriptome
microRNA
PRDM1
Plasma cell differentiation
Humans
Gene Regulatory Networks
Transcription factor
Regulation of gene expression
Multidisciplinary
Gene Expression Profiling
NF-kappa B
Computational Biology
Cell Differentiation
Healthy Volunteers
Cell biology
Gene expression profiling
Repressor Proteins
MicroRNAs
Gene Expression Regulation
Multigene Family
Positive Regulatory Domain I-Binding Factor 1
Transcription Factors
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....daf2012e9e4365ee46f9dfa6bf25224f