Polycomb Repressive Complex 2 Regulates Genes Necessary for Intestinal Microfold Cell (M Cell) Development
| Autor: | George, Joel Johnson, Oittinen, Mikko, Martin-Diaz, Laura, Zapilko, Veronika, Iqbal, Sharif, Rintakangas, Terhi, Arrojo Martins, Fábio Tadeu, Niskanen, Henri, Katajisto, Pekka, Kaikkonen, Minna U., Viiri, Keijo |
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| Přispěvatelé: | Tampere University, BioMediTech, Tays Research Services, Clinical Medicine, Molecular and Integrative Biosciences Research Programme, Doctoral Programme in Integrative Life Science, Centre of Excellence in Stem Cell Metabolism, Doctoral Programme in Biomedicine |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Esrrg
MECHANISM GP2 glycoprotein 2 receptor FAE follicle-associated epithelium Mice Peyer's Patches ENR500 epidermal growth factor Noggin R-spondin 500 ng/mL media 3123 Gynaecology and paediatrics INFECTION Rank receptor activator of nuclear factor κB LTβR lymphotoxin-β receptor TRANSCRIPTION RT-qPCR reverse-transcription quantitative polymerase chain reaction Intestinal Mucosa WENRC media Wnt epidermal growth factor Noggin R-spondin Chir media Original Research PP Peyer’s patch 318 Medical biotechnology Receptor Activator of Nuclear Factor-kappa B NF-kappa B Polycomb Repressive Complex 2 Cell Differentiation RankL receptor activator of nuclear factor κB ligand PRC2 DIFFERENTIATION ERR ChIP-seq chromatin immunoprecipitation sequencing Signal Transduction EPITHELIAL M-CELLS PBS phosphate-buffered saline INHIBITION NF-κB nuclear factor-κB RankL RELB FACTOR SPI-B Gro-seq global run-on sequencing Animals HISTONE H3 KO knockout Microfold Cells Gene Expression Profiling Esrrg estrogen-related receptor γ RANK Ligand Epithelial Cells ENRI media epidermal growth factor Noggin R-spondin Wnt inhibitor IWP2 media M cell Microfold cell GALT gut-associated lymphoid tissue Gene Expression Regulation 3121 General medicine internal medicine and other clinical medicine 3111 Biomedicine Gut Immunity Biomarkers PRC2 polycomb repressive complex 2 |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology |
| Popis: | Background & Aims Microfold cells (M cells) are immunosurveillance epithelial cells located in the Peyer’s patches (PPs) in the intestine and are responsible for monitoring and transcytosis of antigens, microorganisms, and pathogens. Mature M cells use the receptor glycoprotein 2 (GP2) to aid in transcytosis. Recent studies have shown transcription factors, Spi-B and SRY-Box Transcription Factor 8 (Sox8). are necessary for M-cell differentiation, but not sufficient. An exhaustive set of factors sufficient for differentiation and development of a mature GP2+ M cell remains elusive. Our aim was to understand the role of polycomb repressive complex 2 (PRC2) as an epigenetic regulator of M-cell development. Estrogen-related–receptor γ (Esrrg), identified as a PRC2-regulated gene, was studied in depth, in addition to its relationship with Spi-B and Sox8. Methods Comparative chromatin immunoprecipitation and global run-on sequencing analysis of mouse intestinal organoids were performed in stem condition, enterocyte conditions, and receptor activator of nuclear factor κ B ligand–induced M-cell condition. Esrrg, which was identified as one of the PRC2-regulated transcription factors, was studied in wild-type mice and knocked out in intestinal organoids using guide RNA's. Sox8 null mice were used to study Esrrg and its relation to Sox8. Results chromatin immunoprecipitation and global run-on sequencing analysis showed 12 novel PRC2 regulated transcription factors, PRC2-regulated Esrrg is a novel M-cell–specific transcription factor acting on a receptor activator of nuclear factor κB ligand–receptor activator of nuclear factor κB–induced nuclear factor-κB pathway, upstream of Sox8, and necessary but not sufficient for a mature M-cell marker of Gp2 expression. Conclusions PRC2 regulates a significant set of genes in M cells including Esrrg, which is critical for M-cell development and differentiation. Loss of Esrrg led to an immature M-cell phenotype lacking in Sox8 and Gp2 expression. Transcript profiling: the data have been deposited in the NCBI Gene Expression Omnibus database (GSE157629). Graphical abstract |
| Databáze: | OpenAIRE |
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