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Prmt5 is essential for intestinal stem cell maintenance and homeostasis
Li Yang1,2, Xuewen Li1,2, Chenyi Shi1
1State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China.
Cell Regeneration (London, England)
|February 5, 2025
Summary
Protein arginine methyltransferase 5 (Prmt5) is crucial for intestinal stem cell renewal and homeostasis. Its absence causes stem cell deficiency and spontaneous colitis, highlighting Prmt5
Area of Science:
- Gastroenterology
- Epigenetics
- Stem Cell Biology
Background:
- Intestinal homeostasis depends on intestinal stem cells (ISCs).
- Epigenetic regulation is implicated in ISC renewal.
- The role of protein arginine methyltransferase 5 (Prmt5) in intestinal homeostasis is unclear.
Purpose of the Study:
- To investigate the function of Prmt5 in maintaining intestinal homeostasis.
- To elucidate the molecular mechanisms by which Prmt5 regulates ISCs.
Main Methods:
- Utilized mouse models with Prmt5 deletion in the intestinal epithelium.
- Analyzed ISC populations, cell localization, and tissue inflammation.
- Investigated epigenetic modifications, including H3K27ac and Hdac9 expression.
- Examined the effect of histone deacetylase inhibition on Prmt5-depleted ISCs.
Main Results:
- Prmt5 is highly expressed in mouse intestinal crypts.
- Prmt5 deletion led to ISC deficiency, Paneth cell mislocalization, and spontaneous colitis.
- Prmt5 maintains ISC stemness by inhibiting Hdac9 expression and sustaining H3K27ac levels.
- Histone deacetylase inhibition rescued ISC self-renewal and differentiation in Prmt5-depleted cells.
Conclusions:
- Prmt5 is essential for intestinal stem cell function and tissue homeostasis.
- Prmt5 acts as a critical epigenetic regulator in the intestinal epithelium.
- Targeting Prmt5 or related pathways may offer therapeutic strategies for intestinal diseases.
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