Notch signalling regulates asymmetric division and inter-conversion between lgr5 and bmi1 expressing intestinal stem cells.
Journal Article (Journal Article)
Rapidly cycling LGR5+ intestinal stem cells (ISCs) located at the base of crypts are the primary driver of regeneration. Additionally, BMI1 expression is correlated with a slow cycling pool of ISCs located at +4 position. While previous reports have shown interconversion between these two populations following tissue injury, we provide evidence that NOTCH signaling regulates the balance between these two populations and promotes asymmetric division as a mechanism for interconversion in the mouse intestine. In both in vitro and in vivo models, NOTCH suppression reduces the ratio of BMI1+/LGR5+ ISCs while NOTCH stimulation increases this ratio. Furthermore, NOTCH signaling can activate asymmetric division after intestinal inflammation. Overall, these data provide insights into ISC plasticity, demonstrating a direct interconversion mechanism between slow- and fast-cycling ISCs.
Full Text
Duke Authors
Cited Authors
- Srinivasan, T; Than, EB; Bu, P; Tung, K-L; Chen, K-Y; Augenlicht, L; Lipkin, SM; Shen, X
Published Date
- May 16, 2016
Published In
Volume / Issue
- 6 /
Start / End Page
- 26069 -
PubMed ID
- 27181744
Pubmed Central ID
- 27181744
Electronic International Standard Serial Number (EISSN)
- 2045-2322
International Standard Serial Number (ISSN)
- 2045-2322
Digital Object Identifier (DOI)
- 10.1038/srep26069
Language
- eng