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Updated: Apr 29, 2026
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Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
Published on: July 27, 2022
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YY1 is indispensable for Lgr5+ intestinal stem cell renewal
Ansu O Perekatt1, Michael J Valdez1, Melanie Davila1
1Department of Genetics, Human Genetics Institute of New Jersey, Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ 08854; and.
Summary
The transcription factor YY1 is crucial for intestinal stem cell renewal and energy metabolism. Its loss disrupts normal cell turnover, leading to increased proliferation and apoptosis, ultimately proving fatal.
Area of Science:
- Gastroenterology
- Molecular Biology
- Stem Cell Biology
Background:
- Intestinal stem cells drive high tissue turnover and are implicated in disease.
- Understanding their regulation is vital for intestinal health and disease research.
Purpose of the Study:
- To investigate the role of the transcription factor YY1 in intestinal stem cell renewal and homeostasis.
- To elucidate the molecular mechanisms underlying YY1's function in the intestine.
Main Methods:
- Utilized genetic manipulation to delete the Yy1 gene in intestinal cells.
- Analyzed changes in cell turnover, stem cell populations (Lgr5+), proliferation, differentiation, and apoptosis.
- Investigated YY1's role in metabolic regulation via mitochondrial gene expression.
Main Results:
- YY1 deletion disrupted intestinal homeostasis, increasing crypt cell proliferation and decreasing differentiated progeny.
- Loss of YY1 led to a decrease in Lgr5+ stem cells, increased differentiation, and elevated apoptosis.
- YY1 directly binds to mitochondrial complex I genes, and its loss reduces their transcript levels, impacting stem cell metabolism.
Conclusions:
- The transcription factor YY1 is essential for intestinal stem cell renewal and maintaining normal tissue homeostasis.
- YY1 plays a critical role in regulating intestinal stem cell energy metabolism through mitochondrial gene expression.
- Disruption of YY1 function leads to fatal intestinal dysfunction.
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