The stemness of neural crest cells and their derivatives

Abstract

Neural crest cells (NCCs) are unique to vertebrates and emerge from the border of the neural plate and subsequently migrate extensively throughout the embryo after which they differentiate into many types of cells. This multipotency is the main reason why NCCs are regarded as a versatile tool for stem cell biology and have been gathering attention for their potential use in stem cell based therapy. Multiple sets of networks comprised of signaling molecules and transcription factors regulate every developmental phase of NCCs, including maintenance of their multipotency. Pluripotent stem cell lines, such as embryonic stem cells and induced pluripotent stem (iPS) cells, facilitate the induction of NCCs in combination with sophisticated culture systems used for neural stem cells, although at present, clinical experiments for NCC-based cell therapy need to be improved. Unexpectedly, the multipotency of NCCs is maintained after they reach the target tissues as tissue neural crest stem cells (NCSCs) that may contribute to the establishment of NCC-derived multipotential stem cells. In addition, under specific culture conditions, fate-restricted unipotent descendants of NCCs, such as melanoblasts, show multipotency to differentiate into melanocytes, neurons, and glia cells. These properties contribute to the additional versatility of NCCs for therapeutic application and to better understand NCC development.

Germ layers, the neural crest and emergent organization in development and evolution

“…The second line of evidence is the demonstration that stem cells of neural crest origin are present in tissues such as periodontal ligament, dental pulp, and eyes in adults (see Dupin & Sommer, ; Kaltschmidt, Kaltschmidt, & Widera, ; Kunisada, Tezulka, Aoki, & Motohashi, for overviews of the evidence that these cells have the properties of stem cells). Such stem cells, presumed to have originated in the neural crest, offer a cellular basis for the formation of cells in unexpected positions and from unexpected germ layers discussed above.…”

Xenopus ADAM19 regulates Wnt signaling and neural crest specification by stabilizing ADAM13

“…Deficiencies in NC development are a major cause of human birth defects, ranging from relatively subtle craniofacial abnormalities to more severe diseases such as CHARGE and DiGeorge syndromes (Bronner and Simões-Costa, 2016;Mayor and Theveneau, 2013). NC-based cell therapies are also being developed to repair tissues that are damaged by injuries or deteriorate with age (Kunisada et al, 2014;Zhu et al, 2016). Understanding the basic mechanisms that control the specification of NC lineage is crucial for developing new methods to prevent NCrelated birth defects and to regenerate NC-derived tissues for clinical applications.…”

Regulation of viability, differentiation and death of human melanoma cells carrying neural stem cell biomarkers: a possibility for neural trans-differentiation

“…NSC are commercially available and could be easily cultured in serum-free media supplemented with EGF (20 ng/ml), FGF2 (20 ng/ml) and insulin (5 μg/ml). Melanoblasts are known as potentially multipotent cells that could differentiate not only into melanocytes but occasionally into neurons and glial cells [42]. U87MG glioblastoma was used as an additional reference cancer cell line with well-established characteristics of gene expression and malignancy.…”

“…A rate of melanocyte proliferation was substantially downregulated in the process of differentiation: terminally differentiated melanocytes are long-living cells with rare cell divisions (one every 143 days) [20]. On the other hand, melanoblasts, maintain multipotency: under specific conditions they can differentiate not only into melanocytes but also into neurons and glial cells [42]. Interestingly, a recent study demonstrates direct conversion of human fibroblasts to functional melanocytes by a combination of over-expressed transcription factors, MITF, SOX10 and PAX3 [65].…”