Our aim is to understand how stem cell fate is controlled at the molecular level during development, tissue homeostasis and in disease.
The epithelial of the skin and intestine epithelia rely on stem cells for their constant and life-long replenishment. It remains unknown when and how these stem cell first appears during development, how stem cell behaviour is regulated during steady state homeostasis, and to what extent these regulatory mechanisms are altered during regeneration and disease. Insight into these questions will be pivotal for a mechanistic understanding of tissue maintenance, establish cell sources for regenerative therapies and identify new therapeutic targets.
The main objective of the Jensen group is using state-of-the-art quantitative approaches to address these outstanding questions.
Assessing cell fate during tissue morphogenesis
- Analysis of the fetal intestine allowed us to identify and characterize a progenitor state that precedes adult stem cells
- These fetal progenitors retain the potential to mature into adult stem cells, and cells isolated from the small intestine can convert into the cellular identity of colonic epithelium. We believe that this cell culture model constitutes a paradigm for understanding tissue maturation and tissue regionalization.
- Quantitative fate mapping in combination with biophysical modelling enabled us to demonstrate that all cells in the fetal small intestine can become adult stem cells, if placed in the right environment. This has widespread implications as this supports that stem cell identity is an induce property.
Characterising cell behavior during tissue regeneration
- Characterisation of cells during tissue regeneration in the colon have allowed us to demonstrate pronounced changes in cellular identity.
- Regeneration induces cellular dedifferentiation from an adult homeostatic state to a fetal-like state that can be propagated in vitro and also induced using defined media composition.
- The mechanosensors YAP and TAZ are required and sufficient for induction of cellular dedifferentiation and they are essential for tissue regeneration.
Controlling cell behavior during tissue homeostasis
- Define how stem cells become specified during development
- Understand the molecular regulatory machinery that controls stem cell behaviour
- Characterise how stem cell identity is altered during regeneration and disorders, such as inflammatory bowel disease, and identify the molecular mechanisms that govern these changes
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
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
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
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. Cell Stem Cell 13, 734-744
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