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Related Concept Videos

Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

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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.
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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...
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Aryl Hydrocarbon Receptor Activation Coordinates Mouse Small Intestinal Epithelial Cell Programming.

Xiaoliang Zhou1, Debopriya Chakraborty2, Iain A Murray2

  • 1Department of Veterinary and Biomedical Sciences and The Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania; Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Laboratory Investigation; a Journal of Technical Methods and Pathology
|April 11, 2023
PubMed
Summary

The aryl hydrocarbon receptor (AHR) reprograms intestinal cells, influencing their function and promoting resilience. Dietary AHR ligands reshape the gut

Keywords:
Ah receptorICZMath1broccoliindolo[3,2b]carbazoleintestine

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Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Immunology

Background:

  • Intestinal homeostasis relies on cellular turnover, proliferation, differentiation, and self-renewal.
  • The aryl hydrocarbon receptor (AHR) plays a role in adapting to environmental pressures.
  • Understanding AHR's function is crucial for maintaining gut health and resilience.

Purpose of the Study:

  • To investigate the role of the aryl hydrocarbon receptor (AHR) in small intestinal gene expression.
  • To determine how AHR influences intestinal epithelial cell proliferation, differentiation, and remodeling.
  • To explore the impact of AHR signaling on intestinal barrier function and resilience.

Main Methods:

  • Analysis of AHR gene/protein expression gradients within the small intestine.
  • Genetic ablation of Ahr in mice (Ahr-/-) to assess its impact on intestinal cells.
  • Dietary manipulation with and without AHR ligands in wild-type mice (Ahr+/+).

Main Results:

  • Ahr ablation impairs Paneth and goblet cell differentiation, reducing mucin production and barrier function.
  • Ahr-/- mice exhibit increased crypt proliferation and enterocyte exfoliation.
  • Dietary AHR ligands rescue Ahr deficiency phenotypes, while ligand deprivation mimics Ahr deficiency.

Conclusions:

  • AHR is critical for adaptive reprogramming of intestinal gene expression, promoting epithelial resilience.
  • Ligand-induced AHR activity drives goblet cell differentiation, with Math1 identified as a direct target.
  • Dietary cues, mediated by AHR, can significantly reshape the gastrointestinal tract's cellular composition.