Detecting and quantifying clonal selection in somatic stem cells

Detecting and quantifying clonal selection in somatic stem cells
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检测和量化成体干细胞的克隆选择

DOI:
10.1101/2021.12.15.472780
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发表时间:
2021
期刊:
--
影响因子:
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通讯作者:
Körber V
Körber V
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作者:
Körber V

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随着 DNA 变体在体干细胞中积累、被选择或中性进化,它们最终可能会改变组织功能。稳态组织中选择何时以及如何发生尚不完全清楚。在这里,我们介绍了 SCIFER,这是一种可扩展的方法,可以识别单个组织中的选择,而无需了解潜在的驱动事件。此外,SCIFER 还可推断组织干细胞的自我更新和突变动态,如果存在选择,还可推断最大选定克隆的大小和生长速度。我们使用已发表的数据对 SCIFER 进行基准测试,然后对 22 名非白血病个体的骨髓进行克隆性造血 (CH) 检测,识别具有已知和未知驱动事件的 CH。出乎意料的是,我们发现与年龄匹配的非 CH 个体相比,CH 中所有干细胞的分裂加速,这表明骨髓环境改变了 CH 个体的干细胞动力学。 SCIFER 广泛适用于更新体细胞组织以检测和量化选择。
As DNA variants accumulate in somatic stem cells, become selected or evolve neutrally, they may ultimately alter tissue function. When, and how, selection occurs in homeostatic tissues is incompletely understood. Here, we introduce SCIFER, a scalable method that identifies selection in an individual tissue, without requiring knowledge of the underlying driver event. Moreover, SCIFER infers the self-renewal and mutation dynamics of the tissue’s stem cells, and, if selection is present, the size and growth rate of the largest selected clone. We benchmark SCIFER with published data and then probe bone marrow of 22 non-leukemic individuals for clonal hematopoiesis (CH), identifying CH with known and unknown driver events. Unexpectedly, we find accelerated division of all stem cells in CH, compared to age-matched non-CH individuals, suggesting that the bone marrow environment alters stem cell dynamics in individuals with CH. SCIFER is broadly applicable to renewing somatic tissues to detect and quantify selection.
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