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Cellular behavior in space differs significantly from that on Earth. The phenomena such as reduced proliferation and increased apoptosis have been widely reported. However, how microgravity affects the "dormant" state of cells, particularly liver cells which are vital functional cells, remains a mystery.
A study published in NPJ microgravity and led by Dr. LEI Xiaohua from the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences investigated the behavior and molecular changes of liver cells under simulated microgravity conditions.
Researchers revealed that under simulated microgravity conditions, some liver cells detached from the culture surface and formed suspended spheroids. The fates of adherent and suspended cells differed markedly: Suspended cells showed reduced proliferation, decreased apoptosis, and a state akin to "dormancy."
Mechanistic investigations revealed a significant upregulation of the PI3K/AKT/mTOR signaling pathway in adherent cells, accompanied by an increased expression of the downstream protein c-Myc. In contrast, this pathway was less active in suspended cells. Gene manipulation experiments confirmed that silencing c-Myc promoted liver cell detachment, while overexpressing c-Myc prevented it.
These findings indicate that the PI3K/AKT/mTOR pathway and c-Myc play pivotal roles in regulating whether liver cells enter a dormant state under microgravity conditions. This study provides a new perspective on the adaptive mechanisms of cells in space environments, contributing to strategies aimed at protecting astronauts from liver dysfunction, and it provides insights into ground-based medical research on liver cell dormancy-related diseases, including tumor resistance and tissue repair.