Krüppel-like Factor 4 Modulates Development of BMI1+ Intestinal Stem Cell-Derived Lineage Following γ-Radiation-Induced Gut Injury in Mice

• Main Authors: Jes G. Kuruvilla, Chang-Kyung Kim, Amr M. Ghaleb, Agnieszka B. Bialkowska, Calvin J. Kuo, Vincent W. Yang
• Format: Article
• Language: English
• Published: Elsevier 2016-06-01
• Series: Stem Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S221367111630039X

Summary: In response to ionizing radiation-induced injury, the normally quiescent intestinal stem cells marked by BMI1 participate in the regenerative response. Previously, we established a protective role for Krüppel-like factor 4 (KLF4) in the intestinal epithelium where it reduces senescence, apoptosis, and crypt atrophy following γ-radiation-induced gut injury. We also described a pro-proliferative function for KLF4 during the regenerative phase post irradiation. In the current study, using a mouse model in which Klf4 is deleted from quiescent BMI1+ intestinal stem cells, we observed increased proliferation from the BMI1+ lineage during homeostasis. In contrast, following irradiation, Bmi1-specific Klf4 deletion leads to decreased expansion of the BMI1+ lineage due to a combination of reduced proliferation and increased apoptosis. Our results support a critical role for KLF4 in modulating BMI1+ intestinal stem cell fate in both homeostasis and the regenerative response to radiation injury. : Yang and colleagues investigated the function of KLF4 in modulating fate of the BMI1+ intestinal stem cells (ISCs). They show that KLF4 restricts proliferation of normally quiescent BMI1+ ISCs at homeostasis but promotes expansion of the BMI1+ lineage during the regenerative phase after radiation-induced gut injury. These results demonstrate a context-dependent nature of KLF4 in modulating ISC lineage determination.