GSE175809
TGF-ß signaling controls neural crest developmental plasticity via SMAD2/3 [hiNCC RNA-seq]
The neural crest is a highly plastic stem cell population that represents a notable exception to the germ layer theory. Despite being of ectodermal origin, these cells can differentiate into skeletal derivatives like cartilage and bone, tissues that are typically formed by mesoderm. The inductive program that endows the neural crest with these unique properties is still poorly understood. Here, we report that Smad2/3-mediated TGFß signaling endows cranial neural crest cells with enhanced developmental potential. Our results show that TGFß signaling modulates neural crest axial identity and directly activates the gene circuits that support skeletal differentiation. Cooperation between TGFß and low levels of WNT-signaling in the embryonic head activates cranial-specific cis-regulatory elements of anterior genes. Activation of the TGFß pathway allowed reprogramming of trunk neural crest cells to adopt an anterior identity and led to the development of an improved protocol for the generation of human cranial neural crest cells. Our findings indicate TGFß signaling is required for the specification of cranial neural crest cells, endowing them with the potential to give rise to the craniofacial skeleton. Overall design: Examination of transcriptome of human embryonic stem cells and human induced neural crest cells under different differentiation conditions