biostudies-literatureMatsuda YMEXT | Japan Society for the Promotion of ScienceMinistry of Health, Labour and WelfareU.S. Department of Energye2216550120https://www.ebi.ac.uk/biostudies/studies/S-EPMC10104525biostudies-literatureUnknown120(15)Spectra and frequencies of spontaneous and X-ray-induced somatic mutations were revealed with mouse long-term hematopoietic stem cells (LT-HSCs) by whole-genome sequencing of clonal cell populations propagated in vitro from single isolated LT-HSCs. SNVs and small indels were the most common types of somatic mutations, and increased up to twofold to threefold by whole-body X-irradiation. Base substitution patterns in the SNVs suggested a role of reactive oxygen species in radiation mutagenesis, and signature analysis of single base substitutions (SBS) revealed a dose-dependent increase of SBS40. Most of spontaneous small deletions were shrinkage of tandem repeats, and X-irradiation specifically induced small deletions out of tandem repeats (non-repeat deletions). Presence of microhomology sProceedings of the National Academy of Sciences of the United States of AmericaSpectra and characteristics of somatic mutations induced by ionizing radiation in hematopoietic stem cells.PMC1010452522K12388Not applicable19K12338Toshishige MKajimura JKato NSatoh YHayashi TNoda ATanabe OHamasaki KYoshida KMatsuda YUchimura AfalseSpectra and characteristics of somatic mutations induced by ionizing radiation in hematopoietic stem cells.Spectra and frequencies of spontaneous and X-ray-induced somatic mutations were revealed with mouse long-term hematopoietic stem cells (LT-HSCs) by whole-genome sequencing of clonal cell populations propagated in vitro from single isolated LT-HSCs. SNVs and small indels were the most common types of somatic mutations, and increased up to twofold to threefold by whole-body X-irradiation. Base substitution patterns in the SNVs suggested a role of reactive oxygen species in radiation mutagenesis, and signature analysis of single base substitutions (SBS) revealed a dose-dependent increase of SBS40. Most of spontaneous small deletions were shrinkage of tandem repeats, and X-irradiation specifically induced small deletions out of tandem repeats (non-repeat deletions). Presence of microhomology s2023-01-01T00:00:00Z2023 Apr2025-04-04T12:44:41.87Z2025-04-04T12:44:41.87ZS-EPMC101045253701819310.1073/pnas.2216550120