Our aim is to understand how stem cell fate is controlled at the molecular level during development, tissue homeostasis and in disease.
The epithelia of the gastrointestinal tract and the skin are subject to continuous renewal throughout adult life. Stem cells residing in specific locations/environments (stem cell niches) are responsible for the life-long cellular replenishment of these tissues. Extrinsic factors provided by the stem cell niche in combination with the intrinsic properties of the stem cells control the balance between expansion of the stem cell pool by self-renewal and commitment to differentiation following exit from the niche. The regulatory mechanisms that control normal homeostasis are compromised during diseases such as cancer, as excessive accumulation of cell fuels tumor growth. During development and tissue regeneration a similar imbalance between gain and loss of cells can be observed to either fuel organ growth or wound healing. Using mouse models, clinical samples from human patients and state of the art cell culture models, we are currently identifying and characterizing the regulatory mechanisms that control cells fate during development, homeostasis and diseases such as cancer.
Main research focus areas include:
1. Defining the behavior of stem cells in development, homeostasis and regeneration
Figure 1: Using fate mapping of cell populations, we are in a quantitative manner assessing cell behavior under different conditions. In these experiments specific cell populations are labeled with fluorescent markers. The tissue is subsequently assessed in order to determine how the progeny contribute to tissue maintenance. The illustration shows how single Lrig1 expressing cells during steady state homeostasis contribute to the maintenance of the infundibulum and the sebaceous gland. Images are adapted from Page et al., 2013.
2. Developing in vitro models for tissue disease
Movie 1: Intestinal epithelial cells seeded in Matrigel form mini-gut structures that can be maintained in vitro. Using these in vitro models from both mouse and human small intestine and colon, we are developing disease models to study human pathologies in a dish. These models are currently used to define disease mechanisms and for drug discovery. Movie is adapted from Fordham et al., 2013.
3. Characterising the regulatory mechanisms that control stem cell fate
Figure 2: Using organoid models from the small intestine from both fetal and adult tissues, we address how specific molecular mechanisms control cell fate in the fetus and in the adult epithelium.
Selected recent publications
Andersen, M.S., Hannezo, E., Ulyanchenko, S., Estrach, S., Antoku, Y., Pisano, S., Boonekamp, K.E., Sendrup, S., Maimets, M., Pedersen, M.T., Johansen, J.V., Clement, D., Feral, C.C., Simons, B.D.*, Jensen, K.B.* (2019) Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states. Nature Cell Biology 21: 924–32
Clevers, H., Conder, R.K., Li, V.S.W., Lutolf, M.P., Vallier, L., Chan, S., Grikscheit, T.C., Jensen, K.B.*, De Coppi, P.* (2019) Tissue-engineering the intestine: the trials before the trials. Cell Stem Cell 24:855-59
Guiu, J., Hannezo, E., Yui, S., Demharter, S., Ulyanchenko, S., Maimets, M., Jørgensen, A., Perlman, S., Lundvall, L., Mamsen, L.S., Larsen, A., Olesen, R.H., Andersen, C.Y., Thuesen, L.L., Hare, K.J., Pers, T.H., Khodosevich, K., Simons, B.D., Jensen, K.B. (2019) Tracing the origin of adult intestinal stem cells. Nature 570: 107–111
Schweiger P.J., Clement, D.L., Page, M.E., Schepeler, T., Zou, X., Sirokmány, G., Watt, F.M. and Jensen, K.B. (2018) Lrig1 marks a population of gastric epithelial cells capable of long-term tissue maintenance and growth in vitro. Scientific Reports 8:15255
Li, Y., Soendergaard, C., Bergenheim, F.H., Aronoff, D.M., Milne, G., Riis, L.B., Seidelin, J.B., Jensen, K.B.* and Nielsen, O.H.* (2018) COX-2–PGE2 signaling impairs intestinal epithelial regeneration and associates with TNF inhibitor responsiveness in Ulcerative Colitis. eBiomedicine 36:497-507
Petersen, N., Frimurer, T.M., Pedersen, M.T., Egerod, K.L., Wewer Albrechtsen, N.J., Holst, J.J., Grapin-Botton, A., Jensen, K.B. and Schwartz, T.W. (2018) Inhibiting RHOA Signaling in mice increases glucose tolerance and numbers of enteroendocrine and other secretory cells in the intestine. Gastroenterology 155:1164-76
Moestrup, K.S., Chen, Y., Schepeler, T., Schweiger, P.J., and Jensen, K.B. (2018) Dietary control of skin lipid composition and microbiome. Journal of Investigative Dermatology 138:1225-1228
Yui, S., Azzolin, L., Maimets, M., Pedersen, M.T., Fordham, R.P., Hansen, S.L., Larsen, H.L., Guiu, J., Alves, M.R.P, Rundsten, C.F., Johansen, J.V., Li, Y., Madsen, C.D., Nakamura, T., Watanabe, M., Nielsen, O.H., Schweiger, P.J., Piccolo, S. and Jensen, K.B. (2018) YAP/TAZ-dependent reprogramming of colonic epithelium links ECM remodeling to tissue regeneration. Cell Stem Cell 22:35-49
Perea, D., Guiu, J., Hudry, B., Konstantinidou, C., Milona, A., Hadjieconomou, D., Carroll, T., Hoyer, N., Natarajan, D., Kallijärvi, J., Walker, J.A., Soba, P., Thapar, N., Cordero, J., Burns, A.J., Jensen, K.B. and Miguel-Aliaga, I. (2017) A new role for the Ret receptor tyrosine kinase in intestinal epithelia. EMBO J 36, 3029-3045
Holmberg, F.E., Pedersen, J., Jørgensen, P., Soendergaard, C., Jensen, K.B. and Nielsen, O.H. (2017) Intestinal barrier integrity and inflammatory bowel disease: Stem cell-based approaches to regenerate the barrier. Journal of Tissue Engineering and Regenerative Medicine
Moestrup, K.S., Andersen, M.S. and Jensen, K.B. (2017) Isolation and in vitro characterization of epidermal stem cells. Methods Mol Biol 1553, 67-83
Schweiger, P.J. and Jensen, K.B. (2016) Modeling human disease using organotypic cultures. Current Opinion in Cell Biology 43, 22-29