Glutamine boosts intestinal stem cell-mediated small intestinal epithelial development during early weaning: Involvement of WNT signaling

Junquan Tian; Yuying Li; Xuetai Bao; Fan Yang; Xiongzhuo Tang; Qian Jiang; Chengbo Yang; Yulong Yin; Kang Yao

doi:10.1016/j.stemcr.2023.05.012

Glutamine boosts intestinal stem cell-mediated small intestinal epithelial development during early weaning: Involvement of WNT signaling

Stem Cell Reports. 2023 Jul 11;18(7):1451-1467. doi: 10.1016/j.stemcr.2023.05.012. Epub 2023 Jun 15.

Authors

Junquan Tian¹, Yuying Li², Xuetai Bao², Fan Yang², Xiongzhuo Tang³, Qian Jiang⁴, Chengbo Yang⁵, Yulong Yin¹, Kang Yao⁶

Affiliations

¹ National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, China; College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410000, China; University of Chinese Academy of Sciences, Beijing 100008, China.
² National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, China; University of Chinese Academy of Sciences, Beijing 100008, China.
³ College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410000, China.
⁴ National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, China; College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410000, China. Electronic address: jiangqian@hunau.edu.cn.
⁵ Department of Animal Science, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
⁶ National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, China; College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410000, China; University of Chinese Academy of Sciences, Beijing 100008, China. Electronic address: yaokang@isa.ac.cn.

Abstract

Early weaning usually causes small intestine epithelial development abnormality, increasing the risk of gastrointestinal diseases. Glutamine (Gln), enriching in plasma and milk, is widely reported to benefit intestinal health. However, whether Gln affects intestinal stem cell (ISC) activity in response to early weaning is unclear. Here, both the early weaning mice and intestinal organoids were used to study the role of Gln in regulating ISC activities. Results showed that Gln ameliorated early weaning-induced epithelial atrophy and augmented the ISC-mediated epithelial regeneration. Gln deprivation disabled ISC-mediated epithelial regeneration and crypt fission in vitro. Mechanistically, Gln augmented WNT signaling in a dose-dependent manner to regulate ISC activity, while WNT signaling blockage abolished the effects of Gln on ISCs. Together, Gln accelerates stem cell-mediated intestinal epithelial development associated with the augmentation of WNT signaling, which provides novel insights into the mechanism by which Gln promotes intestinal health.

Keywords: WNT signaling; early weaning; glutamine; intestinal epithelial development; intestinal stem cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Proliferation
Glutamine*
Intestinal Mucosa / physiology
Intestine, Small
Mice
Stem Cells
Weaning
Wnt Signaling Pathway*

Substances

Glutamine