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Published on: April 1, 2021
Intestinal stem cells promote crypt fission during postnatal growth of the small intestine
Zenab Mustansir Dudhwala1,2, Paul D Hammond3, Gordon S Howarth3,4
1Gastroenterology, Basil Hetzel Institute for Translational Health Research, Woodville South, South Australia, Australia zenab.dudhwala@adelaide.edu.au.
Insights
Intestinal stem cells drive crypt fission, a process peaking in infancy. This relationship, crucial for gut development, is regulated by Wnt-β-catenin signalling.
Area of Science:
- Gastroenterology
- Developmental Biology
- Cell Biology
Background:
- Wnt-β-catenin signalling is vital for maintaining intestinal stem cells.
- Crypt fission, a process of crypt splitting, is prominent during early life stages.
Purpose of the Study:
- To investigate the connection between intestinal stem cells and crypt fission.
- To understand how crypt fission dynamics change during infancy and early development.
Main Methods:
- Assessed crypt fission and LGR5+ stem cells in human and rat intestinal samples.
- Utilized microdissection and in situ hybridisation for analysis.
- Blocked Wnt-β-catenin signalling using Dickkopf in rats.
Main Results:
- Crypt fission peaked in infancy, declining with age in both humans and rats.
- Wnt-β-catenin signalling inhibition significantly reduced stem cell numbers and crypt fission.
- Stem cell elevation persisted longer during infancy and childhood in humans.
Conclusions:
- Crypt fission is dependent on intestinal stem cells and Wnt-β-catenin signalling.
- The role of stem cells in crypt fission is masked by their low proliferation rate.
- Distinct signalling mechanisms may regulate stem cells and their progeny.
Objective:
Wnt-β-catenin signalling is essential for intestinal stem cells. Our aim was to investigate the relationship between intestinal stem cells and crypt fission which peaks during infancy.
Design:
Duodenal biopsies were obtained during endoscopy to assess the severity of reflux oesophagitis of 15 infants, children and teenagers, which would not affect the duodenum. Samples of small intestine were also obtained from rats 7-72 days of life. Crypt fission was assessed using microdissection of 100 whole crypts and recording the percentage of bifid crypts. Intestinal LGR5+ stem cells were identified by in situ hybridisation. Rats were treated with Dickkopf to block Wnt-β-catenin signalling.
Results:
Crypt fission peaked during infancy before declining after 3-4 years in humans and after 21 days of life in rats. Occasional mitotic figures were seen in bifid crypts during early fission. Stem cells were elevated for a greater period during infancy and childhood in humans. Clustering of Paneth cells was present around the stem cells at the crypt base. Dickkopf reduced the number of stem cells and crypt fission to 45% and 29%, respectively, of control values, showing dependence of both crypt fission and Lgr5+ stem cells on Wnt signalling. However, Dickkopf did not decrease mitotic count per crypt, indicating a difference in signalling between stem cells and their progeny in the transit amplifying zone.
Conclusion:
Crypt fission peaks during infancy and is dependent on intestinal stem cells. This is relatively hidden by 'a cloak of invisibility' due to the low proliferation of stem cells.
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