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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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Establishment of Human Epithelial Enteroids and Colonoids from Whole Tissue and Biopsy

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Clonal analysis of mouse intestinal epithelial progenitors

M Bjerknes¹, H Cheng

¹Department of Anatomy and Cell Biology, University of Toronto, Toronto, Ontario, Canada. bjerknes@crypt.med.utoronto.ca

Gastroenterology

|December 31, 1998

Summary

This study identifies distinct intestinal epithelial progenitor cell types. Short-lived progenitors generate one to two cell types, while long-lived progenitors give rise to multiple cell types, clarifying intestinal stem cell lineages.

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Area of Science:

Gastrointestinal biology
Stem cell research
Epithelial cell differentiation

Background:

The precise cell lineages from stem cells to differentiated intestinal epithelial cells are not well understood.
The existence and characteristics of intermediate progenitor cell types in the intestinal epithelium remain largely uncharacterized.

Purpose of the Study:

To investigate and characterize the intermediate progenitor cell types within the intestinal epithelium.
To elucidate the lineage relationships between stem cells and differentiated cells in the gut.

Main Methods:

Utilized chemical mutagenesis to create random genetic marks in intestinal epithelial cells via somatic mutation of the Dlb-1 locus.
Isolated intact intestinal epithelium at various time points post-mutagenesis.
Scored the composition, size, and location of resulting mutant clones to track cell lineage progression.

Main Results:

Identified short-lived progenitors (C1, M1, Mix) that yield one or two cell types within days.
Discovered long-lived progenitors, including mucous cell progenitors (M0), columnar cell progenitors (C0), and pluripotential stem cells (S), which persist for months.
Observed that mutant progenitors typically partition into a single daughter crypt during crypt branching and that cells disperse widely despite intercellular junctions.

Conclusions:

Established the existence of distinct short-lived and long-lived progenitor populations in the intestinal epithelium.
Demonstrated that long-lived progenitors (M0, C0, S) are capable of generating all intestinal epithelial cell types.
Provided insights into clonal dispersion patterns during intestinal crypt development and cell migration.