Exogenous L-arginine increases intestinal stem cell function through CD90+ stromal cells producing mTORC1-induced Wnt2b.

Qihang Hou, Yuanyang Dong, Jingxi Huang, Chaoyong Liao, Jiaqi Lei, Youli Wang, Yujiao Lai, Yifei Bian, Yang He, Jingjing Sun, Meng Sun, Qiuyu Jiang, Bo Wang, Zhengquan Yu, Yuming Guo, Bingkun Zhang

Communications biology 2020 Oct 23

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The renewal and repair of intestinal epithelium depend on the self-renewal of intestinal stem cells (ISCs) under physiological and pathological conditions. Although previous work has established that exogenous nutrients regulate adult stem cell activity, little is known about the regulatory effect of L-arginine on ISCs. In this study we utilize mice and small intestinal (SI) organoid models to clarify the role of L-arginine on epithelial differentiation of ISCs. We show that L-arginine increases expansion of ISCs in mice. Furthermore, CD90+ intestinal stromal cells augment stem-cell function in response to L-arginine in co-culture experiments. Mechanistically, we find that L-arginine stimulates Wnt2b secretion by CD90+ stromal cells through the mammalian target of rapamycin complex 1 (mTORC1) and that blocking Wnt2b production prevents L-arginine-induced ISC expansion. Finally, we show that L-arginine treatment protects the gut in response to injury. Our findings highlight an important role for CD90+ stromal cells in L-arginine-stimulated ISC expansion.

Citation

Qihang Hou, Yuanyang Dong, Jingxi Huang, Chaoyong Liao, Jiaqi Lei, Youli Wang, Yujiao Lai, Yifei Bian, Yang He, Jingjing Sun, Meng Sun, Qiuyu Jiang, Bo Wang, Zhengquan Yu, Yuming Guo, Bingkun Zhang. Exogenous L-arginine increases intestinal stem cell function through CD90+ stromal cells producing mTORC1-induced Wnt2b. Communications biology. 2020 Oct 23;3(1):611