Our aim is to understand the physiological role of somatic stem cells in tissue homeostasis and characterise molecular mechanisms that control normal and cancer stem cell behaviour and properties. This will provide additional treatment strategies for diseases such as cancer.
Adult tissues such as the epidermis and the gut are subject to continuous renewal, as cells are lost whilst they carry out routine functions. Stem cells residing in specific locations are responsible for the constant replenishment of these tissues as well as tissue repair following injury. The degree of stem cell contribution to tissue replenishment depends on the specific tissue requirements and is regulated by intrinsic and extrinsic factors including the immediate microenvironment (the stem cell niche). An overall balance in the daily loss of cells by programmed cell death and gain of cells via proliferation ensures tissue homeostasis. The contribution from stem cells to tissue maintenance is therefore tightly regulated, and any imbalance however small will have devastating consequences on long-term homeostasis.
Figure 1: Adult stem cell behaviour is regulated by the immediate microenvironment, the stem cell niche. Homeostasis is governed by a carefully balanced contribution from the stem cell compartment.
Stem cells are found in discrete stem cell niches, which impact on stem cell behaviour. The common expression of certain stem cells markers such as Lrig1 between different tissues strongly suggests that components of the stem cell niche are shared between different organs. Moreover, stem cell markers such as Lrig1 are also expressed in cancers indicating that the specific microenvironments that allow stem cell maintenance is recreated in disease.
Figure 2: Stem cells in the skin are found in specialised microenvironments where they are surrounded by other types of cell. This constitutes the stem cell niche.
We are investigating the process of homeostasis and the regulation of adult stem cells with the aim to identify regulatory factors that control stem cell behaviour and are involved in the development of diseases such as cancer. Specifically we are studying:
1. Role of stem cells in development, homeostasis and regeneration
2. The relationship between adult stem cells and cancer
3. Mechanisms that control stem cell behaviour
Figure 3: Lrig1 constitutes a master regulator of stem cell proliferation and controls homeostasis within multiple epithelial stem cell compartments.
Fordham, R.P., Yui, S., Hannan, N.R.F., Soendergaard, C., Madgwick, A., Schweiger, P.J., Nielsen, O.H., Vallier, L., Pedersen, R.A., Nakamura, T. Watanabe, M. and Jensen, K.B. (2013) Transplantation of expanded fetal intestinal progenitors contributes to colon regeneration after injury. In press Cell Stem Cell
Page, M.E., Lombard, P., Ng, F., Göttgens, B. and Jensen, K.B. (2013) The epidermis is comprised of autonomous compartments maintained by distinct stem cell populations. Cell Stem Cell 13, 471-82
Wong VWY, Stange DE, Page ME, Buczacki S, Wabik A, Itami S, van de Wetering M, Poulsom R, Wright NA, Trotter MWT, Watt FM, Winton DJ, Clevers H and Jensen KB (2012) Lrig1 controls intestinal stem cell homeostasis by negative regulation of ErbB signalling. Nature Cell Biology 14, 401-40
Fordham RP and Jensen KB (2012) Reporting Live from the Epidermal Stem Cell Compartment. Cell Stem Cell 11, 141-142
Wong VWY and Jensen KB (2012) Environmental stimuli and intestinal stem cell behavior. Cell Cycle 11, 2767 – 2768
Jensen KB, Driskell RR and Watt FM. (2010) Assaying proliferation and differentiation capacity of stem cells using disaggregated adult mouse epidermis. Nature Protocols, 5, 898-911
Watt FM and Jensen KB. (2009). Epidermal stem cell diversity and quiescence. EMBO Mol Med 1, 260-267
Jensen KB, Collins CA, Nascimento E, Tan DW, Frye M, Itami S and Watt FM (2009). Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis. Cell Stem Cell, 4, 427-439