Long noncoding RNAs in B-cell development and activation

Abstract

Long noncoding RNAs (lncRNAs) are potentially important regulators of cell differentiation and development, but little is known about their roles in B lymphocytes. Using RNA-seq and de novo transcript assembly, we identified 4516 lncRNAs expressed in 11 stages of B-cell development and activation. Most of these lncRNAs have not been previously detected, even in the closely related T-cell lineage. Comparison with lncRNAs previously described in human B cells identified 185 mouse lncRNAs that have human orthologs. Using chromatin immunoprecipitation-seq, we classified 20% of the lncRNAs as either enhancer-associated (eRNA) or promoter-associated RNAs. We identified 126 eRNAs whose expression closely correlated with the nearest coding gene, thereby indicating the likely location of numerous enhancers active in the B-cell lineage. Furthermore, using this catalog of newly discovered lncRNAs, we show that PAX5, a transcription factor required to specify the B-cell lineage, bound to and regulated the expression of 109 lncRNAs in pro-B and mature B cells and 184 lncRNAs in acute lymphoblastic leukemia.

Discovery and validation of immune-associated long non-coding RNA biomarkers associated with clinically molecular subtype and prognosis in diffuse large B cell lymphoma

“…By first separating DLBCL patients of the discovery cohort into either GCB or ABC subtypes based on their clinical information, we performed a comparative analysis for lncRNA expression pattern across GCB and ABC subtypes and uncovered 156 novel differentially expressed lncRNAs associated with either GCB or ABC subtypes. Several recent studies have shown that lncRNA were widely expressed during B-cell development and different lncRNAs played differential functional roles in distinct stages of B-cell development [23, 24]. Our finding has presented evidence that there was differentiated lncRNA expression pattern between GCB and ABC DLBCL, implicating that these subtype-specific lncRNAs may provide additional information for DLBCL subtype classification and prognosis.…”

“…Our previous work has indicated the prognostic roles of lncRNAs in DLBCL patients [22]. Furthermore, recent studies demonstrated that lncRNA expression patterns can characterize distinct stages of B-cell development and activation [23, 24]. However, the expression pattern and clinical implication of lncRNAs between GCB and ABC DLBCL remain unclear.…”

B1 and B2 B cells are characterized by distinct CpG modification states at DNMT3A-maintained enhancers

“…Indeed, many prior studies of CpG methylomes in adult somatic tissues have found that variably methylated regions are strongly enriched at enhancer sites. Analysis of publicly available ChIP-Seq data for H3K4me1 and H3K4me3 modifications in mature B2 and B1 B cells 22 , showed that the DMRs that underwent developmental demethylation in both B1 and B2 B cells colocalized with H3K4me1 peaks in mature B1 and B2 B cells, suggesting that these DMRs might represent developmentally demethylated enhancers that modulate lineagespecific gene expression ( Figure 2C). To assess the significance of these enhancers in the context of hematopoietic development, we also examined H3K4me1 and H3K4me3 marks in HSCs using published ChIP-Seq data.…”

“…We obtained H3K4me1, H3K4me3 ChIP-Seq data in B1 and B2 cells (GSE72017) and H3K4me1 ChIP-Seq data in mouse HSCs (GSE63276) from the NCBI GEO database 22,67 . The ATAC-Seq libraries were generated and sequenced in our laboratory as previously described 40 .…”

The emerging role of long non‐coding RNA in spinal cord injury

“…It has been shown that many lncRNAs are present in neutrophils and the levels of lncRNA expression are associated with development, differentiation and activation of neutrophils [72,73]. Furthermore, previous studies have identified lncRNAs expressed in B lymphocytes and T lymphocytes development and activation [74,75]. Panzeri et al suggested that long intergenic non-coding RNAs could be novel drivers of human lymphocyte differentiation [76].…”