Scientists in Shanghai have discovered a genetic "switch" that can make the liver "repair itself" quickly. Yesterday, the international authoritative academic journal Cell? China Academy of Sciences Center for Excellence and Innovation in Molecular Cell Science (Institute of Biochemistry and Cell Science) returned the stem cells published by the research group. It is found that the Arid 1a protein in the nucleus regulates the "regeneration gene" of hepatocytes in a pre-opened "standby" state in normal hepatocytes, so that hepatocytes can respond to damaged signals more quickly and activate the "regeneration program" of the liver. This study reveals the molecular basis of liver injury and regeneration mediated by hepatocyte reprogramming at the gene level, which provides a new idea for drug-targeted treatment of liver injury.

The liver is one of the most important organs in the human body. Because of its metabolic detoxification function, it is often destroyed by various foreign substances, which leads to a serious decline in the regenerative ability of the liver. It is of great significance to study the regeneration of liver injury and its molecular regulation mechanism.

In recent years, it has been found that hepatocyte reprogramming is the main way to realize hepatocyte regeneration when portal vein liver injury occurs. Hepatocytes are developed and differentiated from hepatic precursor cells. After most cells differentiate, their fate is fixed. However, in liver injury, liver cells are plastic, which can be traced back to liver-like precursor cells similar to liver precursor cells by "reverse growth" and "secondary development" into more newborn liver cells to participate in liver regeneration. However, why liver cells can "grow backwards" has always been an unsolved mystery.

In this study, the researchers found that a chromosome remodeling protein called Arid 1a regulates the "reverse growth" of hepatocytes. After the gene encoding this protein is knocked out, liver cells will not "grow backwards" after liver injury, resulting in defects in liver regeneration. Further research found that the protein can open the "reverse growth" program in liver cells, so when there is a regeneration signal, the "reverse growth" program can be activated, so that differentiated liver cells can be remolded into liver precursor cells in vivo like plasticine. This discovery provides a possible way to control the "reverse growth" of hepatocytes in the future.

Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Dr. He Qiang and Dr. Yang are the first authors, researcher Hui of Molecular Cell Center, researcher and associate researcher of Institute of Nutrition and Health. This work has been strongly supported by the Xie research group of the Long March Hospital affiliated to the Second Military Medical University. The research was supported by China Academy of Sciences, National Natural Science Foundation of China, Ministry of Science and Technology and Shanghai Science and Technology Commission.