Abstract
The neural crest (NC) is a multipotent cell population which can give rise to a vast array of derivatives including neurons and glia of the peripheral nervous system, cartilage, cardiac smooth muscle, melanocytes and sympathoadrenal cells. An attractive strategy to model human NC development and associated birth defects as well as produce clinically relevant cell populations for regenerative medicine applications involves the in vitro generation of NC from human pluripotent stem cells (hPSCs). However, in vivo, the potential of NC cells to generate distinct cell types is determined by their position along the anteroposterior (A–P) axis and, therefore the axial identity of hPSC-derived NC cells is an important aspect to consider. Recent advances in understanding the developmental origins of NC and the signalling pathways involved in its specification have aided the in vitro generation of human NC cells which are representative of various A–P positions. Here, we explore recent advances in methodologies of in vitro NC specification and axis patterning using hPSCs.
Highlights
Human pluripotent stem cells have become a powerful resource to study embryonic development, circumventing both the technical and ethical obstacles associated with the use of human embryos
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 the case for their human pluripotent stem cells (hPSC)-derived counterparts
Increasing concentrations of retinoic acid (RA) results in increased expression of posterior HOX genes, this occurs at the expense of neural crest (NC) markers such as SOX10 [83,86]. Similar to their in vivo counterparts, vagal NC cells generated through these protocols have been shown to further differentiate, via culture in neurotrophic media, toward various components of the enteric nervous system (ENS) including distinct enteric neuronal subtypes marked by expression of 5HT, GABA and NOS [82,83,85,86]
Summary
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. Similar to their in vivo counterparts, vagal NC cells generated through these protocols have been shown to further differentiate, via culture in neurotrophic media, toward various components of the ENS including distinct enteric neuronal subtypes marked by expression of 5HT, GABA and NOS [82,83,85,86].
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