PCGF6 activates SOX2 and contributes to lineage differentiation of human pluripotent stem cells. PCGF6 activates SOX2 and contributes to lineage differentiation of human pluripotent stem cells

To assess and distinguish the molecular role of PCGF6 in the self-renewal and early differentiation of PSCs, we established PCGF6-knockout PSCs. Although the absence of PCGF6 could maintain self-renewal and colony-formation capacity, it induced abnormal early differentiation in PSCs. PCGF6 deficiency in PSCs promoted the development of mesendoderm, and impaired the development of neuroectoderm during differentiation process in vitro. RNA-seq and ChIP-seq experiments revealed that PCGF6 plays different roles in distinct lineage specification. On the one hand, PCGF6 worked as a transcription activator that maintain early neuroectoderm differentiation by regulating the expression of SOX2. On the other hand, PCGF6 resists skewed differentiation toward mesendoderm through the PRC1-dependent inhibition of WNT/β-catenin signaling pathways. Overall design: We performed RNA-seq and PCGF6 ChIP-seq using PSC (two replicates for each), Ub Chip-seq using PSC (only one replicates for each).