Reactivation of the pluripotency program precedes formation of the cranial neural crest

During development, cells progress from a pluripotent state to a more restricted fate within a particular germ layer. However, cranial neural crest cells (CNCCs), a transient cell population that generates most of the craniofacial skeleton, have much broader differentiation potential than their ectodermal lineage of origin. Here, we identify a neuroepithelial precursor population characterized by expression of canonical pluripotency transcription factors that gives rise to CNCCs and is essential for craniofacial development. Pluripotency factor Oct4 is transiently reactivated in CNCCs and is required for the subsequent formation of ectomesenchyme. Furthermore, open chromatin landscapes of Oct4(+) CNCC precursors resemble those of epiblast stem cells, with additional features suggestive of priming for mesenchymal programs. We propose that CNCCs expand their developmental potential through a transient reacquisition of molecular signatures of pluripotency.

Automated summary

A neuroepithelial precursor population characterized by pluripotency transcription factors is essential for craniofacial development, giving rise to cranial neural crest cells. Through transient reactivation of the pluripotency factor Oct4, cranial neural crest cells expand their developmental potential to differentiate into mesenchymal cells. The open chromatin landscapes of Oct4(+) CNCC precursors resemble those of epiblast stem cells, suggesting priming for mesenchymal programs.