Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor, expressed in villus cells of the intestinal epithelium, that promotes cellular differentiation and tissue homeostasis. Previous studies suggest that BMI1^＋ cells represent secretory progenitors with reserve intestinal stem cell (rISC) activity. However, it has not been elucidated how KLF4 contributes to crypt regeneration originated from BMI1^＋ rISC lineage during homeostasis. In this study, Bmi1-Cre^ER;Rosa26^eYFP (Bmi1 ^Ctrl ) and Bmi1-Cre^ER;Rosa26^eYFP;Klf4^fl/fl (Bmi1 ^ΔKlf4 ) mice were injected with tamoxifen to label BMI1＋ cells and their lineage and to delete Klf4. During homeostasis, MUC2^＋ goblet cells appeared in the BMI1^＋ cell lineage 2, 3 and 7 days after tamoxifen administration. After Klf4 deletion in BMI1^＋ cells, the number of KLF4^＋ and MUC2^＋ cells in eYFP^＋ cells decreased in Bmi1 ^ΔKlf4 mice compared with Bmi1 ^Ctrl mice. Thus, KLF4 was positively correlated with goblet cell differentiation in BMI1^＋ cell derived lineage. In ex-vivo analysis, organoids derived from single eYFP^＋ cells of Bmi1 ^Ctrl mice contained MUC2-expressing cells that co-expressed KLF4. On the other hand, organoids derived from Klf4-deleted eYFP^＋ cells from Bmi1 ^ΔKlf4 mice showed reduced number of MUC2-expressing cells. In conclusion, these results suggest that KLF4 regulates goblet cell differentiation in BMI1^＋ ISC-derived lineage during homeostasis.

中文翻译：

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在稳态过程中，KLF4调节BMI1 +中的杯状细胞分化+保留肠道干细胞谱系。

Krüppel样因子4（KLF4）是锌指转录因子，在肠上皮的绒毛细胞中表达，可促进细胞分化和组织动态平衡。先前的研究表明，BMI1 ^＋细胞代表具有储备肠干细胞（rISC）活性的分泌祖细胞。然而，尚未阐明KLF4在稳态过程中如何促进源自BMI1 ^＋ rISC谱系的隐窝再生。在这项研究中，Bmi1- Cre ^ER ; Rosa26 ^eYFP（Bmi1 ^Ctrl）和Bmi1- Cre ^ER ; Rosa26 ^eYFP ; Klf4 ^{fl / fl}（Bmi1 ^向ΔKlf4 ）小鼠注射他莫昔芬标记BMI1 +细胞及其谱系并删除Klf4。在他莫昔芬给药后第2、3和7天，在稳态中，MUC2 ⁺杯状细胞出现在BMI1^＋细胞谱系中。后KLF4缺失BMI1 ⁺细胞，KLF4的数量⁺和MUC2 ⁺细胞EYFP ⁺细胞下降的Bmi1 ^ΔKlf4小鼠相比Bmi1的^Ctrl键小鼠。因此，在BMI1^＋细胞衍生的谱系中，KLF4与杯状细胞分化呈正相关。在离体分析中，类器官来源于单个eYFP Bmi1 ^Ctrl小鼠的^＋细胞含有共表达KLF4的MUC2表达细胞。在另一方面，源自类器官KLF4 -deleted EYFP ⁺细胞的Bmi1 ^ΔKlf4小鼠表现出降低的MUC2表达细胞的数目。总之，这些结果表明，KLF4在体内平衡过程中调节BMI1 ^＋ ISC衍生谱系中的杯状细胞分化。