The neural crest is a versatile population of stem cells found in a developing embryo. In humans, neural crest arises during the third to fourth weeks of pregnancy, and then the cells specialize into a diverse set of cells, including certain types of nerves, skin, bone and muscle. Scientists have long appreciated this crucial event in development – when it goes wrong, a number of skeletal and nervous system disorders can result. But they haven’t really been able to study it properly in the laboratory. That’s because of the transient nature of the neural crest – it typically only exists for about two weeks in humans (with few exceptions). After that, the cells have migrated away and differentiated into other tissue types. Dr. Alexey Terskikh (along with Dr. Marianne Bronner-Fraser at the California Institute of Technology, Sanford-Burnham’s Dr. Evan Y. Snyder, postdoctoral researchers Dr. Carol Curchoe and Dr. Jochen Maurer and others) recently discovered a way to overcome this problem. In a study published recently in the journal PLoS ONE, they developed a new protocol for generating early migratory neural crest cells from human stem cells.
“This new system allows us to dissect what happens during human development – something that is not accessible in any other way,” says Dr. Terskikh, associate professor in Sanford-Burnham’s Development and Aging Program.
Neural crest stem cells are known to produce relatively high levels of one particular gene called Sox10. In this study, the researchers used Sox10 as an identifying marker to separate migrating neural crest stem cells from primitive cell clusters derived from embryonic stem cells. Essentially, they catch Sox10-positive cells as they leave the nest. These migratory neural crest stem cells were then able to spontaneously differentiate into a final tissue type (nerves, muscle, cartilage, etc.) or could be directed to a certain fate with the addition of growth factors.
With this method, Dr. Terskikh’s group and others will now be able to better study what defines human neural crest stem cells, how they migrate during development, how they differentiate into other cell types, and the mechanisms that guide these processes. What’s more, producing workable quantities of neural crest stem cells in the laboratory might allow scientists to generate more of the tissues that they become – including clinically-relevant cell types like skin cells or neurons.
According to Dr. Maurer, one of the study’s co-authors, “This research allows for fast and easy access to an important developmental structure and one of the best examples of a particular stage in development – the epithelial-mesenchymal transition (EMT). Since EMT is now a hot topic in tumorigenesis and cancer progression, these cells might help us better understand the molecular mechanisms governing that process. ”
Curchoe CL, Maurer J, McKeown SJ, Cattarossi G, Cimadamore F, Nilbratt M, Snyder EY, Bronner-Fraser M, & Terskikh AV (2010). Early acquisition of neural crest competence during hESCs neuralization. PloS one, 5 (11) PMID: 21085480