Single cell transcripional analysis of murine adult hepatocytes following YAP induction [Liver_scRNAseq_perfused]

ABSTRACT: YAP1 is a transcriptional co-activator regulated by the Hippo pathway, mechano-transduction, G-protein coupled receptors and WNT signaling. YAP1 activity depends on its stabilization and its nuclear localization. Once in the nucleus, YAP1 can regulate gene expression by interacting with transcription factors with DNA binding capability. While YAP1 main transcriptional partners belong to the TEAD family, several reports indicate that YAP1 can also associate with SMADs, RUNX and other transcription factors. YAP1 acts as a broad regulator of cell growth and differentiation, thus playing a pivotal role in regeneration, re-programming and cancer. How YAP1 may control such a large number of cellular processes is still to be fully understood. To identify how YAP1 controls transcription and to define gene expression programs directly regulated by YAP1, we conducted a genome wide investigation in the mouse liver. Integrated analyses of ChIP-seq and RNA-seq data indicated that YAP1 can act both as an activator and as a repressor in a context dependent way, and allowed the dissection of transcriptional mechanisms. Longitudinal analysis by ChIP-seq and RNA-seq highlighted differences in genome binding and transcriptional control which allowed the identification of acute and tonic YAP1 dependent responses. While during acute activation YAP1 supported cell cycle and signal transduction programs, its prolonged activation sustained a feedforward loop that potentiated and expanded YAP1 dependent transcription thus leading to the direct engagement of cell identity programs. Overall this study provides a genome scale understanding of how YAP1 controls gene expression and reveals principles in gene regulation which account for YAP1 ability to orchestrate development, regeneration and cell reprogramming.

ORGANISM(S): Mus musculus

PROVIDER: GSE138190 | GEO | 2022/07/25

REPOSITORIES: GEO