Detecting and quantifying clonal selection in somatic stem cells.

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

SUBMITTER: Korber V 

PROVIDER: S-EPMC12283403 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature