Prof CAB Jahoda, PhD
Our research interests mainly spring from the developmental biology of embryonic and adult skin and skin appendages. Our aim is to understand fundamental mechanisms in development, but we are applying our knowledge of the developmental biology of skin to investigative dermatology and possible therapeutic solutions using cell and tissue engineering. The research encompasses a diversity of approaches and a wide range of methodologies - from tissue interaction studies, through innovative cell culture techniques, to molecular biology.
Epithelial-Mesenchymal Interactions in the Development and Growth of Skin and Integumental Appendages
This field has is at the core of our research programme and, aside from the hair follicle, includes work on feathers, teeth and other epithelial appendages. We were amongst the first laboratories to describe the inductive potential of discrete populations of follicle dermal cells and to culture specific hair follicle dermal and epithelial cells. In the hair follicle, the relationship of simple patterns of expression to cellular function is not yet well-understood. We have a programme of research that combines our expertise in microsurgery and tissue interaction, and the availability of mutant and transgenic animals with genomic technologies. Current topics of interest include a study into signalling pathways in early hair follicle morphogenesis, and investigating the cellular and molecular basis of dermal condensation formation.
Left: Scanning electon microscopy of basal epidermal cells in developing mouse skin
Right: Syndecan expression in a developing mouse hair follicle
Human Hair Follicle Induction: Application to Transplantation Technology
Stemming from our discovery that cells from the adult hair follicle could induce new follicles in animal skin, there has been keen interest in the idea of using this principle to create new hair follicles for use in human hair transplantation. We previously showed induction of new follicles in human skin following transgender transplantation of follicle dermal cells. Current approaches to transplantation surgery revolve around relocation of a finite number of hair follicles from one site on the scalp to another. Using cellular induction, one could exponentially increase the number of hair follicles by using the body’s own cells to create new ones. Our work focuses on mechanisms required to maintain inductivity in cultured human hair follicle dermal cells.
Transdifferentiation of Epithelial Stem Cells
Building on our developmental experience of inducing hair follicles from skin we have collaborated with Professor Danielle Dhouailly in Grenoble, France to show that adult central cornea cells can be transformed into skin epidermis with hair follicles when subjected to the appropriate inductive dermal source. Subsequently, we have demonstrated that amnion can be similarly transformed into a hair-bearing epidermis. These data provide the basis for investigation into the basic processes of cellular reprogramming and stem cell activity, as well as providing a platform for development of tissue engineered skin substitutes for a diversity of clinical applications. Understanding the mechanisms of epithelial reprogramming allows for application of these principles to regeneration of other epithelial types such as bladder, cornea, intestine, oesophagus, among others.
Adult Hair Growth and Skin Wound Healing - Regeneration and the Production of In Vitro Skin Models and Skin Replacement
Based on findings that demonstrate the regenerative and inductive properties of hair follicle dermal cells, we have postulated that they might also serve as a superior source of donor cells during skin wound healing. We have developed a number of skin equivalent models which use cultured hair follicle dermal cells in place of conventional dermal fibroblast sources. We have shown that these models elicit normal epidermal differentiation. Ultimately our research in this area is directed towards using developmental biology-based tissue engineering approaches to try to create a skin equivalent that will produce hair follicles when grafted in vivo.
Hair Follicle Mesenchymal Progenitor Cells
While our work on epithelial components has focused on transforming other epithelia into skin, our experiments with mesenchymal cells revolves around their potential to generate other cell types. We demonstrated that hair follicle dermis has the potential to repopulate the hematopoietic system in irradiated recipient mice. Further, we have evidence that hair follicle dermal cells can be directed along multiple mesodermal lineages such as adipose and osseous tissue. The accessibility and compartmentalization of hair follicle dermal cells and their potential in recapitulating developmental genetic programmes renders them an attractive source for adult multipotent progenitor cells. Moreover their specialised inductive capabilities make them an interesting model for studying the molecular signals that control the switch between differentiated and progenitor cell status.
Department of Biosciences
- Adult Hair Growth and Skin Wound Healing - Regeneration and the Production of In Vitro Skin Models and Skin Replacement
- Epithelial-Mesenchymal Interactions in the Development and Growth of Skin and Integumental Appendages
- Hair Follicle Mesenchymal Progenitor Cells
- Human Hair Follicle Induction: Application to Transplantation Technology
- Transdifferentiation of Epithelial Stem Cells
- Mardaryev, A.N., Liu, B., Rapisarda, V., Poterlowicz, K., Malashchuk, I., Rudolf, J., Sharov, A.A., Jahoda, C.A., Fessing, M.Y., Benitah, S.A., Xu, G.-L. & Botchkarev, V.A. (2016). Cbx4 maintains the epithelial lineage identity and cell proliferation in the developing stratified epithelium. The Journal of Cell Biology 212(1): 77-89.
- Jahoda, Colin & Gilmore, Adam (2016). What Lies Beneath: Wnt/β-Catenin Signaling and Cell Fate in the Lower Dermis. Journal of Investigative Dermatology 136(6): 1084-1087.
- Higgins, C.A., Chen, J.C., Cerise, J.E., Jahoda, C.A.B. & Christiano, A.M. (2013). Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth. Proceedings of the National Academy of Sciences of the USA 110(49): 19679–19688.
- Higgins, CA, Westgate, GE & Jahoda, CA. (2011). Modulation in proteolytic activity is identified as a hallmark of exogen by transcriptional profiling of hair follicles. Journal of Investigative Dermatology 131: 2349-2357.
- Petukhova, L., Duvic, M. Hordinsky, M. Norris, D. Price, V. Shimomura, Y. Kim, H. Singh, P. Lee, A. Chen, W.V. Meyer, K.C. Paus, R. Jahoda, C.A., Amos, C.I. Gregersen, P.K. & Christiano, A.M. (2010). Genome-wide association study in alopecia areata implicates both innate and adaptive immunity. Nature 466(7302 ): 113-117.
- Higgins, Claire A., Westgate, Gillian E. & Jahoda, Colin A. B. (2009). From telogen to exogen: mechanisms underlying formation and subsequent loss of the hair club fiber. Journal of Investigative Dermatology 129: 2100-2108.
- Richardson, GD, Bazzi, H, Fantauzzo, KA, Waters, JM, Crawford, H, Hynd, P, Christiano, AM & Jahoda, CA (2009). KGF and EGF signalling block hair follicle induction and promote interfollicular epidermal fate in developing mouse skin. Development 136(13): 2153-2164.
- Wojciechowicz, K, Markiewicz, E & Jahoda CA (2008). C/EBPalpha identifies differentiating preadipocytes around hair follicles in foetal and neonatal rat and mouse skin. Experimental Dermatology 17(8): 675-680.
- Reynolds A.J. & Jahoda C.A.B. (2004). Cultured human and rat tooth papilla cells induce hair follicle regeneration and fiber growth. Differentiation 72(9-10): 566-575.
- Jahoda, CAB, Kljuic, A, O'Shaughnessy, R, Crossley, N, Whitehouse, CJ, Robinson, M, Reynolds, AJ, Demarchez, M, Porter, RM, Shapiro, L & Christiano, AM (2004). The lanceolate hair rat phenotype results from a missense mutation in a calcium coordinating site of the desmoglein 4 gene. Genomics 83(5): 747-756.
- Fliniaux I., Viallet J.P. Dhouailly D. & Jahoda C.A.B. (2004). Transformation of amnion epithelium into skin. Differentiation 72: 558-565.
- Kljuic, A, Bazzi, H, Sundberg, JP, Martinez-Mir, A, O'Shaughnessy, R, Mahoney, MG, Levy, M, Montagutelli, X, Ahmad, W, Aita, VM, Gordon, D, Uitto, J, Whiting, D, Ott, J, Fischer, S, Gilliam, TC, Jahoda, CAB, Morris, RJ, Panteleyev, AA, Nguyen, VT & Christiano, AM (2003). Desmoglein 4 in hair follicle differentiation and epidermal adhesion: Evidence from inherited hypotrichosis and acquired pemphigus vulgaris. Cell 113(2): 249-260.
- Jahoda, CAB, Whitehouse, CJ, Reynolds, AJ & Hole, N (2003). Hair follicle dermal cells differentiate into adipogenic and osteogenic lineages. Experimental Dermatology 12(6): 849-859.
- Gharzi, A., Reynolds A.J. & Jahoda, C.A.B. (2003). Plasticity of hair follicle dermal cells in wound healing and induction. Exp. Dermatol (12): 126-136.
- Whitehouse, C.J., Huckle, J.W. & Reynolds, A.J.and Jahoda C.A.B. (2002). Genes that are differentially expressed in rat vibrissa follicle germinative epithelium in vivo show altered expression patterns after extended organ culture. Exp. Dermatol (11): 542-555.
- Lako, M., Armstrong, L., Cairns, P.M., Harris, S., Hole, N. & Jahoda C.A.B. (2002). Hair follicle dermal cells repopulate the mouse haematopoietic system. Journal of Cell Science 115(20): 3967-3974.
- Busby, W., Cameron, N.R. & Jahoda, C.A.B. (2002). Tissue engineering matrixes by emulsion templating. Polymer international 51(10): 871-881.
- Jahoda, CAB & Reynolds, AJ (2001). Hair follicle dermal sheath cells: unsung participants in wound healing. Lancet 358(9291): 1445-1448.
- Robinson, M., Reynolds, A.J. , Gharzi, A. & Jahoda, C.A.B. (2001). In vivo induction of hair growth by dermal cells isolated from hair follicles after extended organ culture. Journal of Investigative Dermatology 117(3): 596-604.
- Jahoda, C.A.B., Oliver, R.F., Reynolds, A.J., Forrester, J.C., Gillespie, J.W., Cserhalmi-Friedman, P.B., Christiano, A.M. & Horne, K.A. (2001). Trans-species hair growth induction by human hair follicle dermal papillae. Exp. Dermatol 10(4): 229-237.
- Ferraris, C., Chevalier, G., Favier, B., Jahoda, C.A.B. & Dhouailly, D. (2000). Adult corneal epithelium basal cells possess the capacity to activate epidermal, pilosebaceous, and sweat gland genetic programs in response to embryonic dermal stimuli. Development (127): 5487-5495.
- Reynolds, A.J., Lawrence, C., Cserhalmi-Friedman, P.B., Christiano, A.M. & Jahoda C.A.B. (1999). Trans-gender induction of hair follicles. Nature (402): 33-34.
- Reynolds, A.J. & Jahoda, C.A.B. (1996). Hair matrix germinative epidermal cells confer follicle-inducing capabilities on dermal sheath and high passage papilla cells. Development (122): 3085-3094.
- Jahoda, C.A.B., Horne, K.A., Mauger, A., Bard, S. & Sengel, P. (1992). Cellular and extracellular involvement in the regeneration of the rat vibrissa follicle. Development (114): 887-897.
- Reynolds, A.J. & Jahoda, C.A.B. (1992). Cultured dermal papilla cells induce follicle formation and hair growth by transdifferentiation of an adult epidermis. Development (115): 587-593.