Related Experiment Video

Updated: Jul 24, 2025

Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase
10:33

Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase

Published on: October 15, 2018

8.3K

TET2 and TET3 loss disrupts small intestine differentiation and homeostasis

Ihab Ansari1, Llorenç Solé-Boldo2, Meshi Ridnik1

  • 1Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University Medical School, Jerusalem, Israel.

Nature Communications
|July 6, 2023
PubMed

Insights

Tetraplegin 2 and 3 (TET2/3) are crucial for maintaining intestinal homeostasis. Their absence in mice disrupts cell balance, alters DNA methylation, and impacts gut health.

Area of Science:

  • Epigenetics and Genomics
  • Gastroenterology and Developmental Biology

Background:

  • TET2/3 enzymes are known for epigenetic regulation and roles in mouse development.
  • Their specific functions in intestinal cellular differentiation and tissue homeostasis are not well understood.

Purpose of the Study:

  • To investigate the role of TET2/3 in intestinal epithelial cell differentiation and homeostasis.
  • To elucidate the molecular mechanisms underlying TET2/3 function in the gut.

Main Methods:

  • Ablation of TET2/3 in mouse intestinal epithelial cells.
  • Analysis of intestinal histology, cell populations (Paneth, Tuft, Enteroendocrine cells).
  • DNA methylation profiling at enhancers.
  • Pharmacological inhibition of DNA methylation.
  • Microbiome analysis and assessment of inflammatory responses.

Main Results:

  • TET2/3 deletion caused severe intestinal homeostasis imbalance, with loss of Paneth cells and altered Tuft/Enteroendocrine cell numbers.
  • Major DNA methylation changes occurred at enhancers linked to cell fate transcription factors and effector genes.
  • Pharmacological DNA methylation inhibition partially rescued cellular and methylation defects.
  • TET2/3 loss altered the gut microbiome, increasing susceptibility to inflammation.

Conclusions:

  • TET2/3 are critical for establishing and maintaining intestinal crypt homeostasis.
  • DNA demethylation mediated by TET2/3 is essential for normal cell differentiation and gut function.
  • TET2/3 loss impacts gut microbiome and predisposes to inflammation.

More Related Videos

3D Culturing of Organoids from the Intestinal Villi Epithelium Undergoing Dedifferentiation06:40

3D Culturing of Organoids from the Intestinal Villi Epithelium Undergoing Dedifferentiation

Published on: April 1, 2021

4.9K
Protocols for Analyzing the Role of Paneth Cells in Regenerating the Murine Intestine using Conditional Cre-lox Mouse Models07:48

Protocols for Analyzing the Role of Paneth Cells in Regenerating the Murine Intestine using Conditional Cre-lox Mouse Models

Published on: November 21, 2015

17.7K

Related Concept Videos

Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
Renewal of Intestinal Stem Cells01:23

Renewal of Intestinal Stem Cells

The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
2.6K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

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.
2.3K
Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.7K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.9K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.3K