Neural Crest Stem Cells/Progenitors and Their Potential Applications in Disease Therapies

Abstract

The neural crest is a remarkable embryonic population generated transiently during early vertebrate development. Because of their multipotency and extensive migratory capacity, neural crest progenitors harbor stem cell characteristics with self-renewal capacity and contribute to a variety of differentiated cell types from cranio-facial skeletal tissues to peripheral nervous system in the trunk. Multiple molecules including signaling factors, transcription factors and components of migratory machinery are expressed at different stages of neural crest development. Gain- and loss-of -function studies in several vertebrate species have revealed the functional relationship of these molecules and assembled them into a gene regulatory network that define the process of neural crest induction, specification, migration and differentiation. These studies form the fundamental criteria for the subsequent establishment and molecular validation of neural crest stem cells/progenitors derived by various strategies. We present here in vivo and in vitro characterization of neural crest stem cells/progenitors isolated from embryonic, fetal and adult tissues as well as the latest experimental approaches for their derivation from embryonic stem cells, induced pluripotent stem cells and skin fibroblasts. We further provide an overview of the recent development in applying neural crest stem/progenitor cells for the treatment of neural crest-associated diseases. Future work is required to explore the possibility in directing neural crest -derived specific lineages from fibroblasts using transcription factor-mediated reprogramming strategy, characterize the differentiation potential of adult-derived neural crest stem cell from different tissue origin, and use genomic editing approach to correct genetic mutations in patient-derived neural crest stem cells/progenitors for transplantation therapy. These endeavors should further unravel and enhance the therapeutic potential of neural crest stem cells/progenitors in clinical setting.