Cellular reprogramming in vivo initiated by SOX4 pioneer factor activity

• DOI: 10.1038/s41467-024-45939-z
• Publication Date: 2024-02-26T18:04:56Z
• Authors: Takeshi Katsuda; Jonathan H. Sussman; Kenji Ito; Andrew Katznelson; Salina Yuan; Naomi Takenaka; Jinyang Li; Allyson J. Merrell; Hector Cure; Qinglan Li; Reyaz Ur Rasool; Irfan A. Asangani; Kenneth S. Zaret; Ben Z. Stanger
• Keywords: Reprogramming

Tissue damage elicits cell fate switching through a process called metaplasia, but how the starting is silenced and new activated has not been investigated in animals. In culture, pioneer transcription factors mediate "reprogramming" by opening chromatin sites for expression that can attract from cell's enhancers. Here we report SOX4 sufficient to initiate hepatobiliary metaplasia adult mouse liver, closely mimicking initiated toxic liver. lineage-traced cells, assessed timing of SOX4-mediated enhancer versus decommissioning. Initially, directly binds closes hepatocyte regulatory sequences via an overlapping motif with HNF4A, master factor. Subsequently, exerts factor activity open biliary sequences. The results delineate hierarchy which gene networks become reprogrammed under physiological conditions, providing deeper insight into basis transitions