Mechanisms of neural crest stem cell differentiation
The neural crest is a transient tissue of vertebrate embryos that originates at the dorsal aspect of the future spinal cord and consists of multipotent stem cells. Neural crest cells emigrate from the developing neural tube into the embryo and give rise to a large range of diverse cell types and tissues of the postnatal organism. Examples of neural crest derivatives include the autonomic and enteric nervous systems, most primary sensory ganglia, the adrenal medulla, smooth musculature of the cardiac outflow tract and great vessels, craniofacial bone/cartilage, tooth papillae, corneal stroma, and melanocytes.
We have defined a panel of 19 genes, which are abundantly expressed both in embryonic and adult neural crest stem cells, but not in epidermal stem cells (Hu et al, 2006). Work in progress using conditional mutant mice and zebrafish indicate that signature genes play important roles in embryonic development.
According to their location in the bulge of hair follicles we termed adult neural crest stem cells ‘epidermal neural crest stem cells’. The bulge is located in the epidermal outer root sheath of hair follicles and is a well-described niche for epidermal stem cells. Epidermal stem cells generate new hair, skin and sebaceous glands. Thus the bulge is now known to contain at least two types of stem cell, epidermal stem cells and EPI-NCSC. EPI-NCSC emigrate from bulge explants and migrate onto the culture substratum. See for instance www.youtube.com/watch?v=TB-lYIPmz9I. EPI-NCSC are able to give rise to all major neural crest derivatives, including neurons, nerve supporting cells, bone/cartilage cells, smooth muscle cells and melanoyctes. In a mouse model of spinal cord injury, mouse EPI-NCSC transplants caused a significant increase in sensory connectivity and touch perception.
As embryonic remnants in an easily accessible postnatal location EPI-NCSC are attractive candidates for cell replacement therapy and regenerative medicine. Our current research efforts therefore focus on ex vivo expansion of human EPI-NCSC, directed differentiation into medically relevant cell types and conversion into iPS cells.
Oliver Clewes, PhD
Research Associate
Kevin Gillinder, MSc
Research Assistant
Dhanak Ggupta
Student
Linda Julian
Student
Alla Narytnyk, MD
Research Assistant
Neil Rajan, MD
Clinical Research Associate
Eleni Takis
Student