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Front Mol Neurosci
2019 Feb 22;12:39. doi: 10.3389/fnmol.2019.00039.
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Human Pluripotent Stem Cell-Derived Neural Crest Cells for Tissue Regeneration and Disease Modeling.
Srinivasan A
,
Toh YC
.
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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.
FIGURE 1. Overview of in vivo NCC development and derivatives and in vitro derivation of human NCCs and major applications. (A) During gastrulation, the neural plate border is specified by BMP, WNT, FGF, and Notch/Delta signaling from the surrounding neural plate, non-neural ectoderm and mesoderm. NCCs are specified at the neural plate border region and then reside in the dorsal portion of the neural tube. Following neural tube closure, they undergo an epithelial-mesenchymal transition and migrate along the anterior-posterior axis of the embryo to give rise to different derivatives based on the region (cranial, cardiac, vagal, or trunk) (Milet and Monsoro-Burq, 2012b; Simoes-Costa and Bronner, 2015; Gandhi and Bronner, 2018). (B) The major approaches by which human NCCs are derived in vitro from hPSCs and differentiated to selected derivatives. The potential applications of these derivatives in regenerative medicine and disease modeling.
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