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. We performed RNA-seq and PCGF6 ChIP-seq using PSC (two replicates for each), Ub Chip-seq using PSC (only one replicates for each).