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Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells
Memory B cells (MBCs) are long-lived and produce high-affinity, generally, class-switched antibodies. Here, we use a multiparameter approach involving CD27 to segregate naïve B cells (NBC), IgD(+) unswitched (unsw)MBCs and IgG(+) or IgA(+) class-switched (sw)MBCs from humans of different age, sex an...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595102/ https://www.ncbi.nlm.nih.gov/pubmed/33116135 http://dx.doi.org/10.1038/s41467-020-19242-6 |
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author | Moroney, Justin B. Vasudev, Anusha Pertsemlidis, Alexander Zan, Hong Casali, Paolo |
author_facet | Moroney, Justin B. Vasudev, Anusha Pertsemlidis, Alexander Zan, Hong Casali, Paolo |
author_sort | Moroney, Justin B. |
collection | PubMed |
description | Memory B cells (MBCs) are long-lived and produce high-affinity, generally, class-switched antibodies. Here, we use a multiparameter approach involving CD27 to segregate naïve B cells (NBC), IgD(+) unswitched (unsw)MBCs and IgG(+) or IgA(+) class-switched (sw)MBCs from humans of different age, sex and race. Conserved antibody variable gene expression indicates that MBCs emerge through unbiased selection from NBCs. Integrative analyses of mRNAs, miRNAs, lncRNAs, chromatin accessibility and cis-regulatory elements uncover a core mRNA-ncRNA transcriptional signature shared by IgG(+) and IgA(+) swMBCs and distinct from NBCs, while unswMBCs display a transitional transcriptome. Some swMBC transcriptional signature loci are accessible but not expressed in NBCs. Profiling miRNAs reveals downregulated MIR181, and concomitantly upregulated MIR181 target genes such as RASSF6, TOX, TRERF1, TRPV3 and RORα, in swMBCs. Finally, lncRNAs differentially expressed in swMBCs cluster proximal to the IgH chain locus on chromosome 14. Our findings thus provide new insights into MBC transcriptional programs and epigenetic regulation, opening new investigative avenues on these critical cell elements in human health and disease. |
format | Online Article Text |
id | pubmed-7595102 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75951022020-11-10 Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells Moroney, Justin B. Vasudev, Anusha Pertsemlidis, Alexander Zan, Hong Casali, Paolo Nat Commun Article Memory B cells (MBCs) are long-lived and produce high-affinity, generally, class-switched antibodies. Here, we use a multiparameter approach involving CD27 to segregate naïve B cells (NBC), IgD(+) unswitched (unsw)MBCs and IgG(+) or IgA(+) class-switched (sw)MBCs from humans of different age, sex and race. Conserved antibody variable gene expression indicates that MBCs emerge through unbiased selection from NBCs. Integrative analyses of mRNAs, miRNAs, lncRNAs, chromatin accessibility and cis-regulatory elements uncover a core mRNA-ncRNA transcriptional signature shared by IgG(+) and IgA(+) swMBCs and distinct from NBCs, while unswMBCs display a transitional transcriptome. Some swMBC transcriptional signature loci are accessible but not expressed in NBCs. Profiling miRNAs reveals downregulated MIR181, and concomitantly upregulated MIR181 target genes such as RASSF6, TOX, TRERF1, TRPV3 and RORα, in swMBCs. Finally, lncRNAs differentially expressed in swMBCs cluster proximal to the IgH chain locus on chromosome 14. Our findings thus provide new insights into MBC transcriptional programs and epigenetic regulation, opening new investigative avenues on these critical cell elements in human health and disease. Nature Publishing Group UK 2020-10-28 /pmc/articles/PMC7595102/ /pubmed/33116135 http://dx.doi.org/10.1038/s41467-020-19242-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Moroney, Justin B. Vasudev, Anusha Pertsemlidis, Alexander Zan, Hong Casali, Paolo Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells |
title | Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells |
title_full | Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells |
title_fullStr | Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells |
title_full_unstemmed | Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells |
title_short | Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells |
title_sort | integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory b cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595102/ https://www.ncbi.nlm.nih.gov/pubmed/33116135 http://dx.doi.org/10.1038/s41467-020-19242-6 |
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