Heterogeneity and 'memory in stem cell populations

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.