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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

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Published on: April 13, 2015

Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells.

Robert K Montgomery¹, Diana L Carlone, Camilla A Richmond

¹Division of Gastroenterology, Children's Hospital Boston, Boston, MA 02115, USA.

Proceedings of the National Academy of Sciences of the United States of America

|December 22, 2010

Summary

A novel subpopulation of slowly cycling intestinal stem cells (ISCs), marked by mouse telomerase reverse transcriptase (mTert) expression, has been identified. These mTert-expressing cells are crucial for intestinal regeneration and long-term tissue maintenance.

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Area of Science:

Gastroenterology
Stem Cell Biology
Regenerative Medicine

Background:

The intestinal epithelium relies on rapidly cycling Lgr5(+) intestinal stem cells (ISCs) for maintenance.
A hypothesis suggests the necessity of slowly cycling ISCs for genomic stability and injury response.

Purpose of the Study:

To identify and characterize slowly cycling intestinal stem cells.
To determine the role of these cells in intestinal homeostasis and regeneration.

Main Methods:

Identification of slowly cycling ISCs using mouse telomerase reverse transcriptase (mTert) expression.
Analysis of cell distribution along the crypt-villus axis.
Assessment of resistance to tissue injury.
Lineage-tracing studies to track cell fate and contribution to regeneration.

Main Results:

A subpopulation of slowly cycling ISCs expressing mTert was identified.
mTert-expressing cells are distributed similarly to long-term label-retaining cells (LRCs) and exhibit resistance to injury.
Lineage tracing confirmed that mTert(+) cells generate all differentiated intestinal cell types and contribute to long-term regeneration after injury.

Conclusions:

The intestine harbors a population of slowly cycling stem cells, marked by mTert expression.
These mTert(+) stem cells are essential for long-term intestinal tissue maintenance and regenerative responses.
The findings support the existence of a dual stem cell system in the intestine, comprising both rapidly and slowly cycling populations.