Srinivasan Tara, Than Elaine Bich, Bu Pengcheng, Tung Kuei-Ling, Chen Kai-Yuan, Augenlicht Leonard, Lipkin Steven M, Shen Xiling
Department of Biomedical Engineering, Cornell University, Ithaca, New York, 14853, USA.
Departments of Medicine, Surgery and Pathology, Weill Cornell Medical College, New York City, New York, 10021, USA.
Sci Rep. 2016 May 16;6:26069. doi: 10.1038/srep26069.
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.
位于隐窝底部的快速循环LGR5+肠干细胞（ISC）是再生的主要驱动因素。此外，BMI1的表达与位于+4位置的慢循环ISC池相关。虽然先前的报告显示组织损伤后这两种细胞群之间会发生相互转化，但我们提供的证据表明，NOTCH信号通路调节这两种细胞群之间的平衡，并促进不对称分裂，作为小鼠肠道中相互转化的一种机制。在体外和体内模型中，NOTCH抑制会降低BMI1+/LGR5+ ISC的比例，而NOTCH刺激则会增加这一比例。此外，肠道炎症后NOTCH信号通路可激活不对称分裂。总体而言，这些数据为ISC的可塑性提供了见解，证明了慢循环和快循环ISC之间的直接相互转化机制。
