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CURRENT RESEARCH: Stem Cells, Wnt signaling and Tissue Repair (updated Dec 2015)
Roel Nusse
Principal Investigator
Our laboratory is interested in the growth, development and integrity of animal tissues. We study multiple different organs, trying to identify common principles, and we extend these investigations to cancer and injury repair. In most organs, different cell types are generated by stem cells - cells that also make copies of themselves and thereby maintain the tissue. An optimal balance between the number of stem and differentiated cells is essential for the proper function of the organs. Locally-acting signals are important to maintain this balance in a spatially-organized manner and these signals are key to understanding the regulation of growth.
Hepatocyte stem cells (From Wang et al, 2015)
A common theme linking our work together are Wnt signals. Work from many laboratories, including our own, has shown that Wnt proteins are essential for the control over stem cells. How this is achieved is far from clear and is the subject of studies in the lab, both in vivo and in cell culture. In vivo, a particular question we address is how physiological changes, such as those occurring during hormonal stimuli, injury or programmed tissue degeneration have an impact on the self-renewal signals and on stem cell biology.
In recent work, we have described a novel population of Wnt-responsive cells in the liver that act as hepatocyte stem cells. These cells are present pericentrally in the liver lobule, express the Wnt target gene Axin2 and can be followed over time to contribute to the entire hepatocyte population in the lobule. Importantly, these cells are diploid, unlike the mostly polyploid mature hepatocytes, and are not dependent on injury and thereby distinct from oval cells and Lgr5 cells. Central vein endothelial cells provide an essential source of Wnt signals and act as a liver stem cell niche (Wang, B., Zhao, L., Fish, M., Logan, C.Y., and Nusse, R. (2015). Self-renewing diploid Axin2(+) cells fuel homeostatic renewal of the liver. Nature 524, 180-185.
Our HHMI website gives an overview of our ongoing research.
PDFs of recent papers can be found here.
All publications (PubMed list).
Roel Nusse
Principal Investigator
Our laboratory is interested in the growth, development and integrity of animal tissues. We study multiple different organs, trying to identify common principles, and we extend these investigations to cancer and injury repair. In most organs, different cell types are generated by stem cells - cells that also make copies of themselves and thereby maintain the tissue. An optimal balance between the number of stem and differentiated cells is essential for the proper function of the organs. Locally-acting signals are important to maintain this balance in a spatially-organized manner and these signals are key to understanding the regulation of growth.
Hepatocyte stem cells (From Wang et al, 2015)
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