Vrije Universiteit Brussel
This project joins 5 research teams with an active interest in the concept of "local stem cell niche" (1;2). This concept will be studied in two organs : liver and pituitary. In the liver, canals of Hering (CoH) and bile ductuli (BD) function as stem cell niche (3;4). The CoV and BD originate in the embryo from the ductal plates. At both sides of the endodermal cell layers of the ductal plate lie mesenchymal cells. Therefore, as from their creation, CoV and BD contain two cell types : an endodermal cuboidal cell type and, peripheral to it, a spindle shaped mesenchymal one. A number of cuboidal cells and some spindle-shaped periductular cells have adult somatic stem cell (ASSC) properties (5;6). In the pituitary, cells of the remaining cleft of the 'Pouch of Ratke' (7) but also folliculo-stellate cells (FS-cells) (8), have been tipped as potential stem-/progenitor cells, but convincing proof is lacking. FS-cells secrete a large number of growth and regulatory factors. Hence, these cells have also been suggested to exert "supporting" functions (9). In the pituitary, the anatomical location that functions as a stem cell niche has not been defined yet. Recently, H. Vankelecom identified by flow cytometry in adult pituitary a "side population" (SP), in which he found high expression of potential stem-/progenitor cell markers (stem cell antigen-1 (Sca-1), Oct-4, Nanog, prominin-1, CD133, Bmi-1), and markers of FS-cells (S100, nestine) Working hypothesis In adult liver, as well as in pituitary, ASSCs are present that have partially or entirely retained their embryonic plasticity. Some of these cells are of endodermal or ectodermal origin. These cells give rise to bile duct epithelial cells or hepatocytes in the liver, and to endocrine cells in the pituitary. Other cells are of mesodermal origin and give rise to stellate cells and sinusoidal fenestrated endothelial cells in the liver, and to FS-cells, nestin+ mesenchymal and fenestrated endothelial cells in the pituitary. To which extent the endodermal/ectodermal and mesenchymal cell compartiments are strictly separated, or whether transdifferentiation is possible, is an important question that will be addressed in this project. The ASSCs stand in close contact with non-stem niche cells and with extracellular matrix. This micro-environment inhibits proliferation and differentiation of ASSCs. Alterations in the micro-environment discontinue this inhibition. References 1.. Ohlstein B, Kai T, Decotto E, Spradling A. The stem cell niche: theme and variations. Curr Opin Cell Biol 2004; 16(6):693-699. 2. Fuchs E, Tumbar T, Guasch G. Socializing with the neighbors: stem cells and their niche. Cell 2004; 116(6):769-778. 3. Theise ND, Saxena R, Portmann BC, Thung SN, Yee H, Chiriboga L et al. The canals of Hering and hepatic stem cells in humans. Hepatology 1999; 30(6):1425-1433. 4. Roskams TA, Theise ND, Balabaud C, Bhagat G, Bhathal PS, Bioulac-Sage P et al. Nomenclature of the finer branches of the biliary tree: canals, ductules, and ductular reactions in human livers. Hepatology 2004; 39(6):1739-1745. 5. Sell S, Ilic Z. Liver Stem cells. Austin, Texas, USA: R.G. Landes Company, 1997. 6. Sell S. The hepatocyte: heterogeneity and plasticity of liver cells. Int J Biochem Cell Biol 2003; 35(3):267-271. 7. Wilson DB. Distribution of 3H-thymidine in the postnatal hypophysis of the C57BL mouse. Acta Anat (Basel) 1986; 126(2):121-126. 8. Horvath E, Kovacs K. Folliculo-stellate cells of the human pituitary: a type of adult stem cell? Ultrastruct Pathol 2002; 26(4):219-228. 9. Allaerts W, Carmeliet P, Denef C. New perspectives in the function of pituitary folliculo-stellate cells. Mol Cell Endocrinol 1990; 71(2):73-81.