So far the knowledge on the early neural development in primates is not well understood due to the restrictions of ethics and material sources. Rhesus monkey embryonic stem cells (rESCs) are ideal candidates for basic research and generation of donor cells for transplantation therapies because the monkey takes advantages over rodents in close genetic and physiological relation to human. This study mainly focused on the neural lineage development with rESCs and the mechanism regulating the migration of glial precursors (GPs). The results are shown as follows:
1. The neuroepithelial stem/progenitor cells (NEPs) derived from rESCs predominantly switched into radial glia (RG) and differentiated into neurons and glia via intermediate neuronal precursors (NPs) and GPs, respectively. Moreover, NEPs/RG pool displayed spatial identity of both dorsoventral and anteroposterior axes of the early neural tube. The maintenance of NEPs/RG was regulated by Notch and FGFR signaling. Additionally, glial restricted precursors (GRPs) were purified, and characterized in vitro and in vivo. The results suggested that the early neural lineage differentiation with rESCs in vitro could essentially mimic the in vivo process and was quite similar to the lineage development in rodents.
2. A2B5+/Nestin-/PSA-NCAM- GPs derived from rESCs initiated to migrate in vitro after NO (released from 10μM—250μM SNP) addition with time-lapse video imaging. Further investigation revealed that Netrin-DCC signaling with Ca2+ involved mediated the cell migration. Besides, Netrin-DCC signaling might combine with extracellualr matrix (ECM) and integrin α6 to cooperatively regulate the migration. It was suggested that NO regulated the migration of the GPs by activating a complex network including Netrin-DCC, Ca2+, ECM and integrin signalings.
This study would facilitate to understand the molecular mechanism of the central nervous system (CNS) development in primates and to provide stage-specific donor cells for therapy on degenerative diseases in the CNS.
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