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Deconstructing the stem cell niche in human interfollicular epidermis in vitro


"Within adult tissues, stem cell properties are heavily influenced by their microenvironment, or niche. In the niche, stem cells integrate a complex array of extrinsic molecular signals that, in concert with cell-intrinsic regulatory networks, control self-renewal and differentiation in response to physiologic demands. By studying adult human epidermal stem cells ex vivo using artificial microenvironments (micro-patterned adhesive islands and hydrogels of differing bulk stiffness) we will investigate two questions: (1) What is the importance of intercellular adhesion in regulating epidermal stem cell fate? (2) How does the genetic state of a stem cell affect its responses to extrinsic signals? Combining state-of-the-art methodologies in biomaterials science and cell biology we will address whether cell-cell and cell-substrate signals have synergistic or antagonist effects on stem cell fate decisions, and whether one type of signal can over-ride another. Specific cell adhesion receptors will be engaged by recombinant proteins bound to latex beads, while specific cell-cell contacts will be engineered via avidin-biotin interaction. We will also investigate how intrinsic modulation of the Notch and Wnt signaling pathways changes epidermal stem cell responses to different niche signals of substrate contact area, substrate porosity and the engagement of specific intercellular adhesion receptors. The proposed project will be carried out at the Centre for Stem Cells & Regenerative Medicine, one of Europe's newest hot spots for stem cell research, based at King's College London, with Prof. Fiona Watt, a world expert in somatic stem cells, as scientist in charge. In such ideal surroundings, the fellow will be able to stimulate and advance European stem cell research, to significantly strengthen his own expertise in skin biology and to add novel research competences, and to establish his own network of collaborations in order to significantly advance his career development."

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WC2R 2LS London
United Kingdom
Rodzaj działalności
Higher or Secondary Education Establishments
Wkład UE
€ 221 606,40
Kontakt administracyjny
Paul Labbett (Mr.)