Heterogeneity and ‘memory’ in stem cell populations
Heterogeneity and ‘memory’ in stem cell populations
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DOI：
10.1088/1478-3975/abba85
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发表时间：
2020-09
期刊：
影响因子：
2
通讯作者：
Patrick S. Stumpf;F. Arai;B. MacArthur
中科院分区：
文献类型：
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作者：
Patrick S. Stumpf;F. Arai;B. MacArthur
现代单细胞实验已经揭示了在明显功能上“纯”的细胞群体中的意想不到的异质性。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的分子状态变化，改变了细胞对未来刺激的反应能力是任何此类理论的重要组成部分。我们通过考虑一个简单的考虑有丝分裂记忆的干细胞增殖的年龄结构模型来说明这一想法。使用这个模型，我们认为，异步有丝分裂产生的异质性是中央干细胞群体功能。这个模型自然地解释了为什么干细胞数量在一生中不断增加，但再生能力同时下降。
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.