Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University, Tampere, Finland.
Institute of Biotechnology, Helsinki Institute of Life Sciences, Helsinki, Finland; Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
Cell Mol Gastroenterol Hepatol. 2021;12(3):873-889. doi: 10.1016/j.jcmgh.2021.05.014. Epub 2021 May 28.
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.
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.
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.
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).
微褶皱细胞（M 细胞）是位于肠道派尔集合淋巴结（PPs）中的免疫监视上皮细胞，负责监测和抗原、微生物和病原体的转胞吞作用。成熟的 M 细胞使用受体糖蛋白 2（GP2）来辅助转胞吞作用。最近的研究表明，转录因子 Spi-B 和性别决定区 Y 框转录因子 8（Sox8）对于 M 细胞分化是必要的，但还不够。一组用于分化和成熟 GP2+M 细胞发育的完整因素仍然难以捉摸。我们的目的是了解多梳抑制复合物 2（PRC2）作为 M 细胞发育的表观遗传调节剂的作用。除了研究其与 Spi-B 和 Sox8 的关系外，还研究了雌激素相关受体 γ（Esrrg）作为 PRC2 调控基因。
在干细胞条件、肠细胞条件和核因子 κ B 受体激活剂配体诱导的 M 细胞条件下，对小鼠肠类器官进行比较染色质免疫沉淀和全基因组 RNA 测序分析。在野生型小鼠和使用向导 RNA 的肠类器官中研究了被鉴定为 PRC2 调控转录因子之一的 Esrrg。使用 Sox8 缺失小鼠研究 Esrrg 及其与 Sox8 的关系。
染色质免疫沉淀和全基因组 RNA 测序分析显示了 12 种新的 PRC2 调控转录因子，PRC2 调控的 Esrrg 是一种新型的 M 细胞特异性转录因子，作用于核因子 κ B 受体激活剂配体-核因子 κ B 受体激活剂诱导的核因子-κ B 途径，在上游 Sox8 之前，是成熟 M 细胞标记物 GP2 表达所必需的，但不是充分的。
PRC2 调节 M 细胞中的一组重要基因，包括 Esrrg，这对于 M 细胞的发育和分化至关重要。Esrrg 的缺失导致 Sox8 和 GP2 表达缺失的不成熟 M 细胞表型。转录谱分析：数据已存入 NCBI 基因表达综合数据库（GSE157629）。
