Shaping axial identity during human pluripotent stem cell differentiation to neural crest cells

Human pluripotent stem cells (hPSCs) have become a powerful resource to study embryonic development, circumventing both the technical and ethical obstacles associated with the use of human embryos. By harnessing the correct developmental signalling pathways during hPSC differentiation, it has become increasingly feasible to generate a vast array of human progenitor cell types with distinct identities and differentiation potential. Combined with the use of patient-derived induced pluripotent stem cells (iPSCs) or CRISPR/Cas9 genome editing, it is possible to use these hPSC derived progenitors in disease modelling or for therapeutic applications such as cell replacement/regenerative medicine therapies. The position of the various cell types that make up the emerging nervous system along the embryonic anteroposterior (A–P) axis is a critical determinant of their functionality, developmental potential and disease vulnerability and an increasing body of evidence has pointed out that this is also the case for their hPSC-derived counterparts. Thus, shaping the desired A–P axial identity in vitro is a crucial aspect in the design of hPSC neural differentiation protocols. The A–P regionalisation of hPSC-derived central nervous system (CNS)-associated cell types has already been discussed in detail in some excellent recent reviews elsewhere [1,2]. Here, we focus on recent findings on the key cellular and signalling parameters directing axial identity acquisition during the transition of hPSCs toward NC cells, the precursors of the peripheral nervous system.