Mammalian organs comprise an extraordinary diversity of cell and tissue types. Following injury, differentiated epithelial cells can serve as a stem cell-independent source for tissue regeneration by undergoing reprogramming into other cell types. However, the intrinsic molecular basis underlying plasticity of differentiated cells remains largely unaddressed.  

A study, conducted by Prof. LI Yixue from the Shanghai Institute of Nutrition and Health and Prof. HUI Lijian from the Shanghai Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, indicated an intrinsic epigenetic basis underlying hepatocyte competence in responding to regenerative signals in injury, which may help us to understand cell plasticity in other epithelial tissues.   

Through constructing Arid1a knockout-out mice of hepatocytes, the researchers discovered that Arid1a deletion inhibited damage repair of liver.

As Arid1a is a key component of the SWI/SNF chromatin remodeling complex, the researchers studied the chromatin open area of liver by ATAC-seq and found that Arid1a helped liver cells to respond quickly to injury-induced signals by endowing a permissive chromatin state of hepatocyte reprogramming genes in the normal condition.

Then they identified the transcription factor Yap in response to Arid1a-mediated hepatocyte reprogramming by combining ChIP-seq and RNA-seq.   

Arid1a facilitated binding of YAP to hepatocyte reprogramming genes, endowing hepatocytes with critical competence in responding the Hippo/Yap signaling pathway in vivo.

These findings provide a framework for studying the contributions of injury-induced LPLCs to periportal liver regeneration.  

This study, published in Cell Stem Cell, was sponsored by the Chinese Academy of Sciences, National Natural Science Foundation of China, the Science and Technology Ministry of China, and Shanghai Science and Technology Committee.

Roles of Arid1a in Injury-induced Liver Reprogramming (Image by Prof. LI Yixue's Group)