MicroRNAs promote neural crest multipotency

Restriction of developmental potential occurs when pluripotent cells undergo gastrulation and germ layer specification. Although cranial neural crest cells are specified from the ectoderm, they are capable of generating both ectodermal and mesodermal lineages. How mammalian neural crest give rise to multiple lineages is not well understood. Here, we use single‐cell ATAC sequencing to characterize chromatin accessibility of cranial neural crest and identify a transient increase in accessibility during specification. This increase in chromatin accessibility coincides with co‐expression of both pluripotency and neural crest transcriptional programs. Analysis of the differentiation trajectory during neural crest specification using single‐cell mRNA sequencing revealed that pluripotent cells of the anterior epiblast resolve into two populations of premigratory cranial neural crest corresponding to ectoderm and mesoderm fates. Our data identify two populations of premigratory cranial neural crest cells that deploy distinct pluripotency programs and rely upon post‐transcriptional gene regulation to expand developmental potential and direct cell fate.