2022
DOI: 10.1038/s41588-022-01035-w
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Single-cell analysis of somatic mutations in human bronchial epithelial cells in relation to aging and smoking

Abstract: While lung cancer risk among smokers is dependent on smoking dose, it remains unknown if this increased risk reflects an increased rate of somatic mutation accumulation in normal lung cells. Here we applied single-cell whole genome sequencing of proximal bronchial basal cells from 33 subjects aged between 11 and 86 years with smoking histories varying from never smoking to 116 pack years. We found an increase in the frequency of single-nucleotide variants and small insertions and deletions with chronological a… Show more

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Cited by 73 publications
(44 citation statements)
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References 60 publications
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“…Interestingly, the association between TML and smoking status which we found finds support along the lines of recent experimental findings linking smoking with an increased risk of LC and a higher frequency of somatic mutations [23]. This association was also suggested by previous preliminar studies [24].…”
Section: Discussionsupporting
confidence: 91%
“…Interestingly, the association between TML and smoking status which we found finds support along the lines of recent experimental findings linking smoking with an increased risk of LC and a higher frequency of somatic mutations [23]. This association was also suggested by previous preliminar studies [24].…”
Section: Discussionsupporting
confidence: 91%
“…Accumulation of genotoxic damage with chronological age is pervasive, and it may also be significantly incremented through lifestyle choices [27, 31, 57, 58]. The fact that augmented DNA damage specifically induces downregulation of long genes is of great interest.…”
Section: Discussionmentioning
confidence: 99%
“…Mutation frequency in cells from smokers increased at a rate of 91 mutations per cell per year, i.e. 3.25X higher [31]. In addition to somatic mutations, exposure to smoke from organic matter is known to provoke TBLs [11], due to benzo[a]pyrene diol epoxide (BPDE) reacting with guanines to form bulky DNA adducts [13].…”
Section: Smoke Exposure Of Human Airways Mimics Age-associated Decrea...mentioning
confidence: 99%
“…Using single-cell approaches, somatic mutation burdens have been found to be substantial and to increase with age, in human brain ( Lodato et al, 2018 ), B lymphocytes ( Zhang et al, 2019 ), liver ( Brazhnik et al, 2020 ), and lung ( Huang et al, 2022 ). The highest numbers of mutations were found in liver, possibly because of the role of this organ in detoxification.…”
Section: Tissue-specific Somatic Mutation Burden As a Function Of Agementioning
confidence: 99%