Rapidly cycling LGR5+ intestinal stem cells (ISCs) located at the base of crypts are the primary driver of regeneration. Additionally, BMI1 expression is correlated with a slow cycling pool of ISCs located at +4 position. While previous reports have shown interconversion between these two populations following tissue injury, we provide evidence that NOTCH signaling regulates the balance between these two populations and promotes asymmetric division as a mechanism for interconversion in the mouse intestine. In both in vitro and in vivo models, NOTCH suppression reduces the ratio of BMI1+/LGR5+ ISCs while NOTCH stimulation increases this ratio. Furthermore, NOTCH signaling can activate asymmetric division after intestinal inflammation. Overall, these data provide insights into ISC plasticity, demonstrating a direct interconversion mechanism between slow- and fast-cycling ISCs.

中文翻译：

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Notch信号调节lgr5和bmi1表达肠干细胞之间的不对称分裂和相互转化。

位于隐窝底部的快速循环的LGR5 +肠干细胞（ISC）是再生的主要驱动力。此外，BMI1表达与位于+4位的ISC慢循环池相关。尽管先前的报告显示了组织损伤后这两个种群之间的相互转化，但我们提供的证据表明，NOTCH信号调节了这两个种群之间的平衡，并促进了不对称分裂，作为小鼠肠内相互转化的一种机制。在体外和体内模型中，NOTCH抑制均会降低BMI1 + / LGR5 + ISC的比例，而NOTCH刺激则会提高该比例。此外，NOTCH信号传导可激活肠道炎症后的不对称分裂。总体而言，这些数据提供了有关ISC可塑性的深刻见解，