体细胞克隆选择的检测和定量，这一成果由牛津大学Thomas Hfer研究组经过不懈努力而取得。相关论文于2025年7月3日发表在《自然—遗传学》杂志上。

研究团队引入SCIFER，这是一种可扩展的方法，可以识别单个组织中的选择，而不需要了解驱动事件。SCIFER还推断出组织干细胞的自我更新和突变动力学，以及所选克隆的大小和年龄。通过探测非恶性人类骨髓和大脑的大量全基因组测序数据，课题组研究人员在这两个组织中发现了普遍的选择。造血过程中选择的克隆，无论是否有已知的驱动因素，都是在整个生命过程中统一启动的。在大脑中，该团队发现了带有胶质瘤起始突变的恶性前克隆和没有已知驱动因素的克隆。与造血相反，大脑中的选择克隆优先起源于童年到青年期。SCIFER广泛适用于体细胞组织的更新检测和量化选择。

研究人员表示，当DNA变异在体细胞中积累、被选择或中性进化时，它们可能最终改变组织功能。选择何时以及如何在体内平衡组织中发生尚不完全清楚。

附：英文原文

Title: Detecting and quantifying clonal selection in somatic stem cells

Author: Krber, Verena, Jakobsen, Niels Asger, Ansari-Pour, Naser, Moore, Rachel, Claudino, Nina, Metzner, Marlen, Thielecke, Eva, Esau, Franziska, Usukhbayar, Batchimeg, Salazar, Mirian Angulo, Newman, Simon, Kendrick, Benjamin J. L., Taylor, Adrian H., Afinowi-Luitz, Rasheed, Gundle, Roger, Watkins, Bridget, Wheway, Kim, Beazley, Debra, Dakin, Stephanie G., Palmer, Antony, Carr, Andrew J., Vyas, Paresh, Hfer, Thomas

Issue&Volume: 2025-07-03

Abstract: 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 driver event. SCIFER also infers self-renewal and mutation dynamics of the tissue’s stem cells, and the size and age of selected clones. Probing bulk whole-genome sequencing data of nonmalignant human bone marrow and brain, we detected pervasive selection in both tissues. Selected clones in hematopoiesis, with or without known drivers, were initiated uniformly across life. In the brain, we found pre-malignant clones with glioma-initiating mutations and clones without known drivers. In contrast to hematopoiesis, selected clones in the brain originated preferentially from childhood to young adulthood. SCIFER is broadly applicable to renewing somatic tissues to detect and quantify selection.

DOI: 10.1038/s41588-025-02217-y

Source: https://www.nature.com/articles/s41588-025-02217-y