Roeland Nusse, PhD, Professor and Chair, Department of Developmental Biology, Stanford University, School of Medicine. Investigator, Howard Hughes Medical Institute
Research Description: Our laboratory is interested in the growth, development and integrity of animal tissues, with a focus on stem cells. Wnt signaling is widely implicated in stem cell control, as a mechanism to regulate the number of stem cells in tissues. We identified Wnt-responsive stem cells by their expression of Axin2 (a common Wnt target gene) and generated a mouse strain with the CreERT2 recombination signal inserted into the Axin2 locus, Axin2-Cre. By clonal labeling, we showed that single stem cells differentiate into different cell types of the tissues of interest. Using this method, we have described novel populations of stem cells in various tissues, including in the liver and the pancreas. In the liver, we found that hepatocytes that reside in the pericentral domain of the liver demonstrate stem cell behavior. They are active in homeostatic cell replacement and therefore distinct from oval cells, which require injury for their induction. Attempts to expand these cells in vitro are under way. Similarly, pancreatic islands contain Axin2-labeled cells that over time differentiate into beta-cells. We have collaborated with Seung Kim’s group over the years in several areas of diabetes research, including foundational studies to develop fruit flies for studies of hormones like insulin, and studies of Wnt regulation of islet beta-cell proliferation.
Selected relevant publications (Stanford DRC members in BOLD):
1. Rulifson, E.J., Kim, S.K., and Nusse, R. (2002). Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science 296, 1118-1120.
2. Rulifson, I.C., Karnik, S.K., Heiser, P.W., ten Berge, D., Chen, H., Gu, X., Taketo, M.M., Nusse, R., Hebrok, M., and Kim, S.K. (2007). Wnt signaling regulates pancreatic beta cell proliferation. Proceedings of the National Academy of Sciences USA 104, 6247-6252.
3. Sugiyama T, Benitez CM, Ghodasara A, Liu L, McLean GW, Lee J, Blauwkamp TA, Nusse R, Wright CV, Gu G, Kim SK. (2013). Reconstituting pancreas development from purified progenitor cells reveals genes essential for islet differentiation. Proc Natl Acad Sci U S A. 110(31):12691-6.