Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Long non-coding RNAs in B cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Jethro Johnson

PROVIDER: E-GEOD-72019 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Long noncoding RNAs in B-cell development and activation.

Brazão Tiago F TF Johnson Jethro S JS Müller Jennifer J Heger Andreas A Ponting Chris P CP Tybulewicz Victor L J VL

Blood 20160705 7

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 ...[more]

PMID: 27381906

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Project description:Background: Although genome-wide association studies (GWAS) have identified hundreds of variants associated with risk of autoimmune and immune-related disorders (AID), our understanding of the diseases mechanisms is limited. In particular, more than 90% of the risk variants lie in non-coding regions, and almost 10% of these map to long non-coding RNA transcripts (lncRNAs). LncRNAs are known to show more cell-type specificity than protein-coding genes. Methods: In this study, we aimed to characterize lncRNAs and protein-coding genes located in loci associated with nine AID which have been well-defined by Immunochip analysis, by transcriptome analysis across seven peripheral blood leukocyte populations (granulocytes, monocytes, NK cells, B-cells, memory-T cells, naive CD4+ and naive CD8+ T-cells) and four cord blood derived T-helper cell populations (precursor, primary, polarized (Th1, Th2) T-helper cells). Results: We show that lncRNAs mapping to loci shared between AIDs are significantly enriched in immune cell types when compared to lncRNAs from the whole genome (M-NM-1<0.005). We were not able to prioritize single cell types relevant for specific diseases, but we observed five cell types enriched (M-NM-1<0.005) in five AID (NK cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis; memory-T and CD8+ T-cells in juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, rheumatoid arthritis; Th0 and Th2 cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, rheumatoid arthritis). Furthermore we show that co-expression analyses of lncRNAs and protein-coding genes can predict the signaling pathways in which these AID-associated lncRNAs are involved. Conclusions: The observed enrichment of lncRNA transcripts in AID loci implies an important role for lncRNAs in AID etiology and suggests that lncRNA genes should be studied in more detail to correctly interpret GWAS findings. The co-expression results strongly support a model in which the lncRNA and protein-coding genes function together in the same pathways. 7 immune cell types

Project description:Macrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and alter their phenotype in response to local environmental cues. While the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes specifically in lung cancer has not been well studied. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multi-marker flow cytometry we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA-seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and express multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor, and selectively express a panel of chemokines genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict good or poor outcome in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and suggest that distinct populations play specific roles in tumor progression. mRNA profiles of macrophage/monocyte cells isolated from murine control or tumor-bearing lung. From naive mice: MacA cells (MacA-N), MacB1 cells (MacB1-N), MacB2 cells (MacB2-N); from 2 week tumor bearing mice: MacA cells (MacA-2wk), MacB2 cells (MacB2-2wk), MacB3 cells (MacB3-3wk); from 3-week tumor bearing mice: MacB2 (MacB2-3wk), MacB3 cells (MacB3-3wk). Each population was analyzed in triplicate (cells were isolated in 3 independent experiments).

Dataset Information

Long non-coding RNAs in B cells

Publications

Long noncoding RNAs in B-cell development and activation.

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