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Published on: May 30, 2012
Myb controls intestinal stem cell genes and self-renewal
Dane Cheasley1, Lloyd Pereira, Sally Lightowler
1Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Stem Cells (Dayton, Ohio)
|October 15, 2011
Summary
Transcription factor Myb is crucial for regulating intestinal stem cell (ISC) gene expression, particularly Lgr5, impacting gastrointestinal epithelium homeostasis and response to injury. Myb
Area of Science:
- Gastroenterology and Stem Cell Biology
- Molecular and Cellular Biology
Background:
- The gastrointestinal tract epithelium's rapid proliferation is tightly regulated during homeostasis and disease.
- Intestinal stem cells (ISCs) are key to epithelial regeneration, and their regulatory mechanisms are under intense study.
Purpose of the Study:
- To investigate the role of transcription factor Myb in regulating intestinal stem cell (ISC) gene expression and function.
- To elucidate the relationship between Myb, Lgr5 expression, and Wnt signaling in ISCs.
Main Methods:
- Analysis of gene expression in wild-type and hypomorphic Myb (plt4/plt4) mice.
- Small intestinal (SI) organoid cultures and self-renewal assays.
- Inducible Myb knockout studies.
- Assessment of gene expression following ionizing radiation (IR).
Main Results:
- Myb directly governs ISC gene expression, notably Lgr5, which is critical for all four lineages in SI organoids and overexpressed in colorectal cancer.
- Myb and Wnt signaling cooperate for maximal Lgr5 promoter activation; plt4/plt4 mice exhibit reduced Lgr5 expression.
- The response of ISC genes to IR is diminished in plt4/plt4 mice, with altered expression of bmi-1, olfm4, and cyclinE1.
- Organoid cultures and inducible Myb knockout confirm ISC dependence on Myb for self-renewal.
Conclusions:
- Transcription factor Myb plays a vital role in maintaining intestinal stem cell (ISC) identity and function.
- Myb is essential for the proper regulation of ISC genes, including Lgr5, and for the response to DNA damage.
- These findings highlight Myb as a critical regulator in stem cell biology with implications for gastrointestinal health and disease.
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