Abstract
Neural crest cells (NCCs) are a multipotent and migratory cell population in the developing embryo that contribute to the formation of a wide range of tissues. Defects in the development, differentiation and migration of NCCs give rise to a class of syndromes and diseases that are known as neurocristopathies. NCC development has historically been studied in a variety of animal models, including xenopus, chick and mouse. In the recent years, there have been efforts to study NCC development and disease in human specific models, with protocols being established to derive NCCs from human pluripotent stem cells (hPSCs), and to further differentiate these NCCs to neural, mesenchymal and other lineages. These in vitro differentiation platforms are a valuable tool to gain a better understanding of the molecular mechanisms involved in human neural crest development. The use of induced pluripotent stem cells (iPSCs) derived from patients afflicted with neurocristopathies has also enabled the study of defective human NCC development using these in vitro platforms. Here, we review the various in vitro strategies that have been used to derive NCCs from hPSCs and to specify NCCs into cranial, trunk, and vagal subpopulations and their derivatives. We will also discuss the potential applications of these human specific NCC platforms, including the use of iPSCs for disease modeling and the potential of NCCs for future regenerative applications.
Highlights
Neural crest cells (NCCs) are transient, migratory stem cells that originate from the neural tube and migrate to different embryonic tissues to give rise to a wide variety of cell types (Le Douarin et al, 2004)
This study demonstrates the great potential of human pluripotent stem cells (hPSCs)-based in vitro assays to identify novel disease-associated mutations with high power
This extensive body of work to induce the formation of NCCs and its derivatives in vitro has enabled the use of hPSC-derived NCCs for applications including disease modeling and tissue regeneration
Summary
Neural crest cells (NCCs) are transient, migratory stem cells that originate from the neural tube and migrate to different embryonic tissues to give rise to a wide variety of cell types (Le Douarin et al, 2004) They form ectodermal derivatives, such as sensory and enteric neurons, Schwann cells, as well as mesenchymal derivatives (Le Douarin and Dupin, 2003). It has been shown that NCC induction at the NPB relies on BMP, WNT, Notch/Delta, and FGF signaling emanating from the surrounding embryonic tissues (Rogers et al, 2012) Based on these molecular developmental programs, researchers have developed increasingly specific and efficient protocols to derive an NCC population from hPSCs in vitro as highlighted below
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