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.

现代单细胞实验揭示了明显功能“纯”细胞群的意外异质性。然而，我们仍然缺乏一个概念框架来理解这种异质性。在这里，我们提出细胞记忆——细胞对刺激做出反应的分子状态变化，改变细胞对未来刺激做出反应的能力——是任何此类理论的重要组成部分。我们通过考虑考虑有丝分裂记忆的干细胞增殖的简单年龄结构模型来说明这一想法。使用这个模型，我们认为异步有丝分裂会产生异质性，这是干细胞群功能的核心。这个模型自然地解释了为什么干细胞数量在一生中增加，但再生能力同时下降。