At the origin of intestinal epithelial stem cells and beyond
Normal adult intestinal stem cells (ISCs) are located within stem cells niches, where the number of stem cells, proliferation within the stem cell compartment and potentially their future cell fate is controlled by niche factors. ISCs are sufficient for life-long replenishment of intestinal epithelia and can fuel tumour growth. Interestingly, the strict hierarchal behaviour observed during steady state homeostasis is bypassed following tissue damage and therapies targeting cancer stem cell.
As cells with stem cell properties are essential for long-term tissue replenishment, it is essential to understand how and when stem cells appear in the intestine, and how cells are regulated at the cellular level upon tissue damage. Using a combination of mouse models and organoid cultures we have recently addressed addres these key questions. Based on simulation of biophysical and behavioural data, we now provide a model for the emergence of adult ISCs during development, where stem cells arise from a pool of equipotent progenitors. Interestingly, this behaviour is recapitulated by cells during regeneration, and we propose that the cellular plasticity observed during tissue regeneration is simply reflecting the return to a more primitive foetal state.
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 21:924-932
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
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
Biotech Research & Innovation Centre - University of Copenhagen
Domain 2 - UMR 3215 / U934 - Genetics and Developmental Biology