On 27th July 2024, Assistant Professor Takeshi Katsuda, Chemical System Engineering, recieved Best Presentation Award, The 31st Japanese Society for the Research of Hepatic Cells.
Assistant Professor Katsuda is third from the right.
Best Presentation Award, The 31st Japanese Society for the Research of Hepatic Cells
About awarded research
Under chronic liver injury, it is known that some hepatocytes undergo reprogramming into biliary cells. However, the epigenetic mechanisms behind this process were largely unknown. On the other hand, insights have been accumulating regarding in vitro reprogramming phenomena. Particularly in the reprogramming of iPS cells, it is known that pioneer transcription factors bind to regions that were originally closed in fibroblasts and open them up, thereby inducing the acquisition of pluripotency. Therefore, in this study, we hypothesized that a similar mechanism might operate in vivo and sought to verify this. Using an adeno-associated virus, we first expressed SOX4, which had been identified in previous research as a potential pioneer factor, in mouse hepatocytes in vivo. We discovered that the cells began to show gene expression and an open chromatin state characteristic of reprogrammed cells, while conversely, they lost characteristics of hepatocytes. Next, we examined which regions of the genome SOX4 binds to at two time points—18 hours and 4 days after viral administration. Interestingly, it was revealed that SOX4 first binds to the enhancers of hepatocytes and suppresses their activity, and later, binds to the enhancers of biliary cells and induces their activity. Furthermore, as a mechanism for enhancer inactivation, we found that the enhancer regions, which had been occupied by HNF4A (the master factor of hepatocytes), were taken over by SOX4. From these findings, it became clear that SOX4 induces the initiation of hepatocyte transdifferentiation into biliary cells by sequentially regulating both the inactivation and activation of enhancers.
Your impression & future plan
We have uncovered a new aspect of pioneer factors. I hope that this research will contribute to further advancements in reprogramming studies. This award provides great motivation for my future research endeavors, and I am deeply grateful.