Heterogeneity and ‘memory’ in stem cell populations

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

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 – the ability of individual cells to record their developmental past and adapt their response to their environment accordingly – are an essential ingredient in any such theory. We illustrate this idea by considering a simple age-structured model of stem cell proliferation. Using this model we argue that heterogeneity is central to stem cell population function, and memories naturally explain 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

   Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 81-858, 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, UK

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

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