Pekka Katajisto

Tissue renewal by adult stem cells is regulated by a multitude of cell intrinsic and extrinsic mechanism, which jointly guide decisions between two cell fates - stem cell self-renewal and differentiation. Interestingly, the microenvironment of stem cells, also called the niche, has often a distinct shape.Recent findings by us and others demonstrate that metabolism can influence cell fate. As metabolites can be exchanged between cells, we hypothesize that fate of tissue stem cells is controlled by metabolism running jointly within the surrounding cellular community, and the geometry of the niche facilitates this communal metabolism. Moreover, age-induced changes in tissue architecture may deregulate metabolite sharing and thereby tissue renewal by stem cells.We will first establish the order of metabolic and transcriptional events during fate change. Second, we assess the extent and impact of metabolite sharing by developing methods capable of detecting exchange of metabolites between two cell types. To study the impact of niche geometry, we will develop artificial scaffolds instructing custom niche topology. Finally, we will characterize the tissue geometry alterations during aging, and probe the possibility to promote tissue regeneration by supporting a youthful geometry via apical constriction of cells.Our work challenges the fundamental concept of cell fate, and has the potential to uncover metabolic tools advancing protocols for future cellular therapies.