Sa1103 – Stem Cell Expansion and Increased Mesenchymal Stem Cell Niche Activity in Human Short Bowel Syndrome

days after tamoxifen injection from Bmi1 Ctrl and Bmi1 hKlf4 mice in Matrigel.There was no significant difference for organoid formation efficiency between Bmi1 Ctrl and Bmi1 hKlf4 .We observed that organoids derived from control YFP + cells were capable of multipotent differentiation and contained MUC2-expressing cells that co-expressed KLF4.However, organoids derived from Klf4-deleted YFP + cells did not produce MUC2-expressing cells.The effect of Klf4 deletion from BMI1 + ISCs on tissue regeneration was evaluated by measuring organoid formation efficiency following 1, 2 and 4 Gy IR (Bmi1 Ctrl , n=3; Bmi1 hKlf4 , n=6).At 5 days post-IR, Klf4-deleted YFP + cells showed a decreased trend of organoid formation efficiency, suggesting that KLF4 protects BMI1 + ISCs against IR-induced injury.Conclusion: These results demonstrate that one of KLF4's functions in BMI1 + ISCs is to maintain a quiescent state during homeostasis.In addition, KLF4 plays a radio-protective role in BMI1 + ISCs.The mechanism by which KLF4 exerts these activities is currently under investigation.