Heterogeneity and ‘memory’ in stem cell populations

Physical Biology, vol. 17, pp. 065013

Abstract

Modern single cell experiments have revealed unexpected heterogeneity in apparently functionally 'pure' cell populations. However, we are still lacking a conceptual framework to understand this heterogeneity. Here, we propose that cellular memories-changes in the molecular status of a cell in response to a stimulus, that modify the ability of the cell to respond to future stimuli-are an essential ingredient in any such theory. We illustrate this idea by considering a simple age-structured model of stem cell proliferation that takes account of mitotic memories. Using this model we argue that asynchronous mitosis generates heterogeneity that is central to stem cell population function. This model naturally explains why stem cell numbers increase through life, yet regenerative potency simultaneously declines.

Authors 3

1. Patrick S. Stumpf Aachen Joint Research Centre for Computational Biomedicine (JRC-COMBINE)

   RWTH Aachen University

   Affiliation as printed

   Joint Research Center for Computational Biomedicine, RWTH Aachen University, Aachen, 52074, Germany

2. Fumio Arai

   Kyushu University

   Affiliation as printed

   Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan

3. Ben D. MacArthur corresponding

   University of Southampton

   Affiliation as printed

   Centre for Human Development, Stem Cells and Regeneration, University of Southampton, SO17 1BJ, United Kingdom

   Institute for Life Sciences, University of Southampton, SO17 1BJ, United Kingdom

   Mathematical Sciences, University of Southampton, SO17 1BJ, United Kingdom