Berlin 2015 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 19: Multi-cellular systems

BP 19.9: Vortrag

Dienstag, 17. März 2015, 12:00–12:15, H 1058

Robust balance of stochastic stem cell fate through revesible differentiation — •Philip Greulich¹ and Benjamin D. Simons^1,2 — ¹TCM Group, Cavendish Laboratory, University of Cambridge, Cambridge, UK — ²Gurdon Institute, University of Cambridge, Cambridge, UK

Adult stem cells are the key players in maintaining healthy tissue. In order to keep the population of cells in a tissue stable, the number of stem cells must stay constant over time, i.e. proliferation and differentiation of stem cells must be perfectly balanced (homeostasis). Otherwise, tissues degenerate or dysplastic lesions develop, which can evolve into cancer. In recent years studies have shown that in many mammalian tissues the stem cell fate (stem cell duplication vs. differentiation) is decided stochastically, with equal chances for gain (duplication) and loss of stem cells (differentiation). Nonetheless, the mechanism to maintain the balance in cell fate outcomes remains largely unknown.

Here I present a non-equilibrium stochastic model for cell fate dynamics, where balance of cell fate outcomes follows automatically from two properties of the cells: (i) the cells' potential to reversibly differentiate independent from cell divisions, (ii) their ability to sense and respond to mechanical cues. The model is able to accurately reproduce experimental cell lineage data of living tissues and, remarkably, shows a high robustness towards failure of regulatory pathways. This mechanism may explain how the stability of the cell population in tissues is maintained, and how robust protection against tumours, despite of high frequency of disrupting mutations, is achieved in living organisms.