Detecting and quantifying clonal selection in somatic stem cells

Verena Körber

doi:10.1038/s41588-025-02217-y

2025-07-03

Mirian Angulo Salazar

Simon Newman

Benjamin Kendrick

Adrian Taylor

Rasheed Afinowi-Luitz

DOI：10.1038/s41588-025-02217-y

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随着DNA变异在体细胞干细胞中积累，经历选择或中性进化，它们最终可能改变组织功能。选择在稳态组织中何时以及如何发生尚不完全清楚。在此，我们介绍SCIFER，一种可扩展的方法，可在不要求了解驱动事件的情况下识别单个组织中的选择。SCIFER还可推断组织干细胞的自我更新和突变动力学，以及选择克隆的大小和年龄。通过探究非恶性人类骨髓和脑部的全基因组测序数据，我们在两种组织中均检测到广泛的选择。在造血系统中，已知或未知驱动因素的选克隆在整个生命过程中均匀启动。在脑部，我们发现携带胶质瘤起始突变的癌前克隆以及无已知驱动因素的克隆。与造血系统不同，脑部中的选择克隆优先起源于儿童期至青年期。SCIFER广泛应用于更新体细胞组织，以检测和量化选择。SCIFER使用群体遗传学模型在全基因组测序数据中检测克隆选择。应用于一系列体细胞组织时，SCIFER量化干细胞动力学，并推断克隆年龄和大小，而不需要了解驱动事件。

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Nature Genetics

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botnar research centre

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German Cancer Research Center (DKFZ)

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Radcliffe Department of Medicine

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