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Renewal of Intestinal Stem Cells01:23

Renewal of Intestinal Stem 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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Inflammatory Bowel Disease II: Crohn's Disease01:30

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Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
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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.
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...
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Inflammatory Bowel Disease I: Ulcerative Colitis01:27

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Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
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Chronic Bowel Disorders: Introduction01:17

Chronic Bowel Disorders: Introduction

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Chronic bowel diseases are a group of long-term conditions affecting the digestive tract, characterized by inflammation and damage to the gut lining. These conditions primarily include irritable bowel syndrome and inflammatory bowel disease.
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
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Chronic Pancreatitis I: Introduction01:24

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The pancreas, an elongated and flat gland situated behind the stomach, serves a vital function in digesting food and managing blood sugar levels.
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
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Related Experiment Video

Updated: Jun 15, 2025

Protocols for Analyzing the Role of Paneth Cells in Regenerating the Murine Intestine using Conditional Cre-lox Mouse Models
07:48

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

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Bottom-up or Top-down: Inflammation Reprograms Paneth Cells to Develop Bowel Cancers.

Julian Chua1,2, Alex Gregorieff3,4,5, Arshad Ayyaz1,2,6

  • 1Department of Biological Sciences, University of Calgary, Calgary, Canada.

Cancer Research
|August 26, 2024
PubMed
Summary

Colorectal cancer may originate from differentiated Paneth cells, not just stem cells, especially with inflammation and a Western diet. This challenges the established stem cell theory for intestinal tumorigenesis.

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Author Spotlight: Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids
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Author Spotlight: Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids
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Area of Science:

  • Gastroenterology
  • Oncology
  • Cell Biology

Background:

  • Colorectal cancer (CRC) origins were debated, with early theories placing origins near the crypt-villus junction.
  • The discovery of Lgr5+ stem cells led to the prevailing theory that CRC arises from stem cells at the crypt base.

Purpose of the Study:

  • To investigate alternative cell lineages as origins for colorectal cancer.
  • To challenge the established paradigm of colorectal cancer initiation from stem cells.

Main Methods:

  • Utilized a study published in Nature Genetics by Verhagen and colleagues.
  • Investigated the role of differentiated nonstem cell lineages in intestinal tumorigenesis.

Main Results:

  • Provided compelling evidence that differentiated Paneth cells can be a source of intestinal tumors.
  • Demonstrated that inflammation and a Western-style diet promote tumorigenesis from these differentiated cells.

Conclusions:

  • Challenges the long-held theory that colorectal cancer exclusively originates from stem cells.
  • Proposes a new paradigm where differentiated cells, particularly Paneth cells, can initiate colorectal cancer, especially under specific dietary and inflammatory conditions.
  • Offers a potential explanation for the rising incidence of colorectal cancer in younger populations.