Epigenetic signature of human vitamin D3 and IL-10 conditioned regulatory DCs
Abstract During differentiation of precursor cells into their destination cell type, cell fate decisions are enforced by a broad array of epigenetic modifications, including DNA methylation, which is reflected by the transcriptome. Thus, regulatory dendritic cells (DCregs) acquire specific epigeneti...
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-79299-x |
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| author | Silvia Liu Alan F. Zahorchak Steven F. Dobrowolski Diana M. Metes Angus W. Thomson Hossam A. Abdelsamed |
| author_facet | Silvia Liu Alan F. Zahorchak Steven F. Dobrowolski Diana M. Metes Angus W. Thomson Hossam A. Abdelsamed |
| author_sort | Silvia Liu |
| collection | DOAJ |
| description | Abstract During differentiation of precursor cells into their destination cell type, cell fate decisions are enforced by a broad array of epigenetic modifications, including DNA methylation, which is reflected by the transcriptome. Thus, regulatory dendritic cells (DCregs) acquire specific epigenetic programs and immunomodulatory functions during their differentiation from monocytes. To define the epigenetic signature of human DCregs generated in vitamin D3 (vitD3) and IL-10 compared to immune stimulatory DCs (sDCs), we measured levels of DNA methylation by whole genome bisulfite sequencing (WGBS). Distinct DNA methylation patterns were acquired by DCregs compared to sDCs. These patterns were located mainly in transcriptional regulatory regions. Associated genes were enriched in STAT3-signaling and valine catabolism in DCregs; conversely, pro-inflammatory pathways, e.g. pattern recognition receptor signaling, were enriched in sDCs. Further, DCreg differentially-methylated regions (DMRs) were enriched in binding motifs specific to the immunomodulatory transcription factor Krueppel-like factor 11 (KLF11), while activator protein-1 (AP-1) (Fos:Jun) transcription factor-binding motifs were enriched in sDC DMRs. Using publicly-available data-sets, we defined a common epigenetic signature shared between DCregs generated in vitD3 and IL-10, or dexamethasone or vitD3 alone. These insights may help pave the way for design of epigenetic-based approaches to enhance the production of DCregs as effective therapeutic agents. |
| format | Article |
| id | doaj-art-792445a8ea6e476e856df477eeebc201 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-792445a8ea6e476e856df477eeebc2012025-08-20T02:22:26ZengNature PortfolioScientific Reports2045-23222024-11-0114111110.1038/s41598-024-79299-xEpigenetic signature of human vitamin D3 and IL-10 conditioned regulatory DCsSilvia Liu0Alan F. Zahorchak1Steven F. Dobrowolski2Diana M. Metes3Angus W. Thomson4Hossam A. Abdelsamed5Pittsburgh Liver Research Center, University of PittsburghDepartment of Surgery, University of PittsburghDepartment of Pathology, University of PittsburghDepartment of Surgery, University of PittsburghPittsburgh Liver Research Center, University of PittsburghPittsburgh Liver Research Center, University of PittsburghAbstract During differentiation of precursor cells into their destination cell type, cell fate decisions are enforced by a broad array of epigenetic modifications, including DNA methylation, which is reflected by the transcriptome. Thus, regulatory dendritic cells (DCregs) acquire specific epigenetic programs and immunomodulatory functions during their differentiation from monocytes. To define the epigenetic signature of human DCregs generated in vitamin D3 (vitD3) and IL-10 compared to immune stimulatory DCs (sDCs), we measured levels of DNA methylation by whole genome bisulfite sequencing (WGBS). Distinct DNA methylation patterns were acquired by DCregs compared to sDCs. These patterns were located mainly in transcriptional regulatory regions. Associated genes were enriched in STAT3-signaling and valine catabolism in DCregs; conversely, pro-inflammatory pathways, e.g. pattern recognition receptor signaling, were enriched in sDCs. Further, DCreg differentially-methylated regions (DMRs) were enriched in binding motifs specific to the immunomodulatory transcription factor Krueppel-like factor 11 (KLF11), while activator protein-1 (AP-1) (Fos:Jun) transcription factor-binding motifs were enriched in sDC DMRs. Using publicly-available data-sets, we defined a common epigenetic signature shared between DCregs generated in vitD3 and IL-10, or dexamethasone or vitD3 alone. These insights may help pave the way for design of epigenetic-based approaches to enhance the production of DCregs as effective therapeutic agents.https://doi.org/10.1038/s41598-024-79299-x |
| spellingShingle | Silvia Liu Alan F. Zahorchak Steven F. Dobrowolski Diana M. Metes Angus W. Thomson Hossam A. Abdelsamed Epigenetic signature of human vitamin D3 and IL-10 conditioned regulatory DCs Scientific Reports |
| title | Epigenetic signature of human vitamin D3 and IL-10 conditioned regulatory DCs |
| title_full | Epigenetic signature of human vitamin D3 and IL-10 conditioned regulatory DCs |
| title_fullStr | Epigenetic signature of human vitamin D3 and IL-10 conditioned regulatory DCs |
| title_full_unstemmed | Epigenetic signature of human vitamin D3 and IL-10 conditioned regulatory DCs |
| title_short | Epigenetic signature of human vitamin D3 and IL-10 conditioned regulatory DCs |
| title_sort | epigenetic signature of human vitamin d3 and il 10 conditioned regulatory dcs |
| url | https://doi.org/10.1038/s41598-024-79299-x |
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