Epidermal Stem Cell Biology

Research overview

Our lab studies the stem cells of adult mammalian epidermis, the outer covering of the skin. The epidermis is a highly tractable system in which to study the properties of adult stem cells in normal tissue homeostasis and in disease. The epidermis is maintained throughout adult life by stem cells, which self-renew and produce progeny that undergo terminal differentiation along the lineages of the hair follicles (HF), sebaceous glands (SG) and interfollicular epidermis (IFE). Several different stem cell populations have now been identified in the IFE, sebaceous gland and hair follicle. Stem cells in each location are functionally interconvertible, but normally give rise to a more restricted repertoire of differentiated cells because of local microenvironmental cues.

We are investigating the following questions:

What is the relationship between different epidermal stem cell populations?
Single cell gene expression profiling and in vivo approaches have uncovered an unexpected heterogeneity in epidermal stem cells. We are using a variety of approaches to determine how many stem cell populations exist within the epidermis and whether or not they are arranged in a hierarchy (Jensen et al., 2009).

What are the microenvironmental cues that regulate whether a stem cell will self-renew or initiate terminal differentiation?
In collaboration with researchers in the University Chemistry Department we have generated engineered micro-patterned substrates that accommodate individual human epidermal stem cells. This allows us to systematically evaluate the effects of multiple parameters of the stem cell microenvironment (Connelly et al., 2010). Complementing these highly synthetic approaches we are examining the consequences of knocking out or overexpressing genes in mice using a variety of strategies. It is clear that interactions between epidermal and mesenchymal cells profoundly affect epidermal homeostasis and we have recently begun to explore fibroblast heterogeneity within the dermis (Driskell et al., 2009).

What are the signalling pathways that regulate differentiation along the different epidermal lineages?
Several core pathways have been identified that regulate epidermal stem cell renewal and lineage selection, including the Wnt and Notch pathways. Current issues under investigation include how different stem cell populations respond to the same signal and the different consequences of applying the same signal but varying signal strength and duration (Berta et al., 2009).

4 key publications

1. Connelly, J.T., Gautrot, J.E., Trappmann, B., Tan, D.W.-M., Donati, G., Huck, W.T.S. and Watt, F.M. (2010) Actin and serum response factor transduce physical cues from the microenvironment to regulate epidermal stem cell fate decisions. Nat. Cell Biol. 12:711-718

2. Berta, M.A., Baker, C.M., Cottle, D.L. and Watt, F.M. (2009) Dose and context dependent effects of Myc on epidermal stem cell proliferation and differentiation. EMBO Molecular Medicine 2:16-25

3. Driskell, R.R., Giangreco, A., Jensen, K.B., Mulder, K. W. and Watt, F.M. (2009) Sox2 positive dermal papilla cells specify hair follicle type in mammalian epidermis. Development 136:2815-2823

4. Jensen, K.B., Collins, C.A., Nascimento, E., Tan, D.W., Frye, M., Itami, S. and Watt, F.M. (2009) Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis. Cell Stem Cell 4: 427-439

Page updated 12 January 2011