To enhance the production efficiency of sows, the utilization of early weaning has been extensively adopted in modern intensive pig farming. Nevertheless, the practice of early weaning commonly causes abnormalities in the small intestinal epithelial function and development of piglets, leading to poor growth performance and even heightened mortality rates. This, in turn, poses a significant financial burden on the pig industry. At present, the comprehension of early weaning-induced small intestinal damage is predominantly limited to the realm of mature small intestinal epithelial cells. Of note, with a renewal cycle of 3-5 days, the small intestinal epithelium in healthy piglets is among the quickest renewing tissues in the body. The regeneration of intestinal epithelium is driven by intestinal stem cells (ISCs) located in the crypt, whereas the mature small intestinal epithelial cells situated on the villi no longer undergo proliferation. However, how early weaning affects the function of ISCs in mediating the development of intestinal epithelium is still unclear.

　　The research team of Professor Yulong Yin from Institute of Subtropical Agriculture, Chinese Academy of Sciences, recently clarified the mechanism underlying early weaning-induced abnormality in the development of small intestinal epithelium from the perspective of ISCs. They found that early weaning depressed the self-renewal of ISCs and attenuated the activity of ISCs-driven intestinal epithelial regeneration and crypt expansion in vivo and ex-vivo. Further results showed that early weaning retarded the differentiation of ISCs into transit-amplifying cells and Paneth cells, and accelerated the apoptosis of villous epithelial cells, jointly leading to intestinal epithelial atrophy. Mechanistically, early weaning inhibited Wnt signaling in ISCs, while an exogenous Wnt amplifier restored ISCs’ function in ex-vivo. They concluded that early weaning depresses the activity of ISCs via attenuating Wnt/β-catenin signaling, thereby impeding ISCs-driven epithelial regeneration. This may provide a basal theory for the development of nutrients targeting stem cells to alleviate early weaning-induced intestinal problems.

　　The Stem Cell Research & Therapy has recently published the study on their online platform. Professor Kang Yao is the responding author of the paper, and Junquan Tian, a doctoral candidate, is the first author of the paper. This work was supported by the National Natural Science Foundation of China (32130099), Key Programs of Frontier Scientific Research of the Chinese Academy of Sciences (QYZDY-SSW-SMC008), and TaiShan Industrial Experts Program (tscy20190121).

　　Paper link: https://stemcellres.biomedcentral.com/articles/10.1186/s13287-023-03293-9

　　Contact: Kang Yao

　　E-mail: yaokang@isa.ac.cn

　　Institute of Subtropical Agriculture, Chinese Academy of Sciences

　　Schematic diagram showing early weaning inhibits the activity of ISCs-driven epithelial regeneration and crypt fission via suppression of Wnt/β-catenin.(Image by Junquan Tian)