a stem cell niche dominance theorem干细胞利基优势定理.pdfVIP

Wolkenhauer et al. BMC Systems Biology 2011, 5:4 /1752-0509/5/4 RESEARCH ARTICLE Open Access A stem cell niche dominance theorem 1,2* 3 4 Olaf Wolkenhauer , Darryl K Shibata , Mihajlo D Mesarović Abstract Background: Multilevelness is a defining characteristic of complex systems. For example, in the intestinal tissue the epithelial lining is organized into crypts that are maintained by a niche of stem cells. The behavior of the system ‘as a whole’ is considered to emerge from the functioning and interactions of its parts. What we are seeking here is a conceptual framework to demonstrate how the “fate” of intestinal crypts is an emergent property that inherently arises from the complex yet robust underlying biology of stem cells. Results: We establish a conceptual framework in which to formalize cross-level principles in the context of tissue organization. To this end we provide a definition for stemness, which is the propensity of a cell lineage to contribute to a tissue fate. We do not consider stemness a property of a cell but link it to the process in which a cell lineage contributes towards tissue (mal)function. We furthermore show that the only logically feasible relationship between the stemness of cell lineages and the emergent fate of their tissue, which satisfies the given criteria, is one of dominance from a particular lineage. Conclusions: The dominance theorem, conceived and proven in this paper, provides support for the concepts of niche succession and monoclonal conversion in intestinal crypts as bottom-up relations, while crypt fission is postulated to be a top-down principle. Background The intestinal crypt serves as an example for a com- The maintenan