Cell Discovery (Feb 2022)

Cross-species metabolomic analysis identifies uridine as a potent regeneration promoting factor

  • Zunpeng Liu,
  • Wei Li,
  • Lingling Geng,
  • Liang Sun,
  • Qiaoran Wang,
  • Yang Yu,
  • Pengze Yan,
  • Chuqian Liang,
  • Jie Ren,
  • Moshi Song,
  • Qian Zhao,
  • Jinghui Lei,
  • Yusheng Cai,
  • Jiaming Li,
  • Kaowen Yan,
  • Zeming Wu,
  • Qun Chu,
  • Jingyi Li,
  • Si Wang,
  • Chunyi Li,
  • Jing-Dong J. Han,
  • Reyna Hernandez-Benitez,
  • Ng Shyh-Chang,
  • Juan Carlos Izpisua Belmonte,
  • Weiqi Zhang,
  • Jing Qu,
  • Guang-Hui Liu

DOI
https://doi.org/10.1038/s41421-021-00361-3
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 22

Abstract

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Abstract Regenerative capacity declines throughout evolution and with age. In this study, we asked whether metabolic programs underlying regenerative capability might be conserved across species, and if so, whether such metabolic drivers might be harnessed to promote tissue repair. To this end, we conducted metabolomic analyses in two vertebrate organ regeneration models: the axolotl limb blastema and antler stem cells. To further reveal why young individuals have higher regenerative capacity than the elderly, we also constructed metabolic profiles for primate juvenile and aged tissues, as well as young and aged human stem cells. In joint analyses, we uncovered that active pyrimidine metabolism and fatty acid metabolism correlated with higher regenerative capacity. Furthermore, we identified a set of regeneration-related metabolite effectors conserved across species. One such metabolite is uridine, a pyrimidine nucleoside, which can rejuvenate aged human stem cells and promote regeneration of various tissues in vivo. These observations will open new avenues for metabolic intervention in tissue repair and regeneration.