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Renewal of Intestinal Stem Cells01:23

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Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Updated: Nov 4, 2025

3D Culturing of Organoids from the Intestinal Villi Epithelium Undergoing Dedifferentiation
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Polycomb Repressive Complex 2 Regulates Genes Necessary for Intestinal Microfold Cell (M Cell) Development.

Joel Johnson George1, Mikko Oittinen1, Laura Martin-Diaz1

  • 1Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University, Tampere, Finland.

Cellular and Molecular Gastroenterology and Hepatology
|May 31, 2021
PubMed
Summary
This summary is machine-generated.

Polycomb repressive complex 2 (PRC2) epigenetically regulates microfold (M) cell development. Estrogen-related receptor gamma (Esrrg) is a novel M-cell transcription factor, essential but not sufficient for mature M-cell development.

Keywords:
EsrrgGut ImmunityMicrofold CellsPRC2RankL

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Area of Science:

  • Immunology
  • Epigenetics
  • Cell Biology

Background:

  • Microfold (M) cells in Peyer's patches are crucial for intestinal immunosurveillance.
  • Mature M cells utilize glycoprotein 2 (GP2) for antigen transcytosis.
  • Spi-B and SRY-Box Transcription Factor 8 (Sox8) are necessary but not sufficient for M-cell differentiation.

Purpose of the Study:

  • Investigate the role of polycomb repressive complex 2 (PRC2) in M-cell development.
  • Identify novel factors sufficient for mature M-cell differentiation.
  • Elucidate the function of Estrogen-related receptor γ (Esrrg) in M-cell development and its relationship with Spi-B and Sox8.

Main Methods:

  • Comparative chromatin immunoprecipitation and global run-on sequencing in mouse intestinal organoids.
  • CRISPR-Cas9 mediated knockout of Esrrg in organoids.
  • Analysis of Sox8 null mice to study Esrrg interactions.

Main Results:

  • Identified 12 novel PRC2-regulated transcription factors.
  • Esrrg is a novel M-cell-specific transcription factor acting upstream of Sox8.
  • Esrrg is necessary but not sufficient for Gp2 expression, a mature M-cell marker.

Conclusions:

  • PRC2 epigenetically regulates key genes, including Esrrg, essential for M-cell development.
  • Loss of Esrrg results in an immature M-cell phenotype lacking Sox8 and Gp2.
  • Esrrg is a critical regulator in the pathway towards M-cell differentiation.