Pluto Bioinformatics

GSE144579: Hippo-YAP signaling controls lineage differentiation of mouse embryonic stem cell through super-enhancers [RNA-seq]

Bulk RNA sequencing

Hippo-YAP signaling pathway is a highly conserved pathway during evolution. It involves in a broad spectrum of physiological and pathological procedure. It also functions in early lineage differentiation of pluripotent stem cells, but the detailed mechanisms remain elusive. Our previous research revealed that knockout of Mst1 and Mst2, the key components of Hippo signaling in mouse embryonic stem cells (ESCs), led ESCs preferentially differentiate into ectoderm lineage, and the differentiation to mesoderm and endoderm lineage was disturbed. To uncover the underlying regulatory mechanisms, we performed ChIP-seq experiments with antibodies against Yap, master transcription factors and some characterized histone modification markers. Combined with RNA-seq assays of wild type and Mst KO ESCs and day 4 embryoid bodies (EBs), we found that YAP is preferentially enriched at Nanog, Sox2, Oct4 and H3K27Ac co-marked super-enhancers (SEs) in ESCs. The upregulation of YAP in Mst KO ESCs resulted in the formation of new super-enhancers on lineage associated genes, leading to the upregulation of these genes and the distortion of ESC differentiation. Hence, our study revealed a super-enhancer related ESC lineage differentiation mechanism which can be shaped by Hippo-YAP signaling. SOURCE: Ren,Zhi,Jun (renzhj5@mail2.sysu.edu.cn) - JKW lab SUN-SEN UNIVERSITY