Our group focuses on adult stem cells of the intestine and the stomach. We try to understand the mechanisms by which these stem cells maintain homeostasis within the tissue, but also how they react upon challenges like inflammation. Furthermore, we are interested in the role of theses stem cells in tumor initiation and tumor growth.
Background – Organoid
Intestinal stem cells have been first identified by the laboratory of Hans Clevers in Utrecht by a specific marker (Lgr5) which is uniquely expressed on this cell type (1). A mouse line expressing a fluorescent mark from the Lgr5 promoter has allowed a detailed molecular analysis of the intestinal stem cell, resulting in the definition of the intestinal stem cell signature (2). Several stem cell specific genes were subsequently shown to be important players in the maintenance of intestinal stem cell homeostasis, such as Ascl2 (3), Lrig1 (4) and Rnf43 (5). A mouse model expressing a fluorescent mark under the promoter of another intestinal stem cell expressed gene, Troy, identified several Troy positive cell populations in different organs of the mouse, including a population of cells at the bottom of gastric glands. Lineage tracing experiments proved the stemness of this cell population (6). In parallel, culture conditions were developed that allowed an outgrowth of single Lgr5 and Troy positive cells into so called organoids, small organ-like 3D structures that contain stem cells and differentiated cells of the organ of origin (7). Variation of culture conditions has also allowed the outgrowth of human intestinal and gastric tissue, including cancers from these organs (8).
(1) Barker et al, Nature, 2005 (2) Munoz*, Stange* et al, EMBO, 2012 (3) van der Flier et al, Cell, 2009 (4) Wong*, Stange* et al, Nat Cell Biol, 2012 (5) Koo et al, Nature, 2012 (6) Stange*, Koo* et al, Cell, 2013 (7) Sato et al, Nature, 2009 (8) Sato et al, Gastroenterology, 2011