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Tracking single-cell evolution using clock-like chromatin accessibility loci

Nature Biotechnol. 2024-05; 
Yu Xiao, Wan Jin, Lingao Ju, Jie Fu, Gang Wang, Mengxue Yu, Fangjin Chen, Kaiyu Qian, Xinghuan Wang & Yi Zhang
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摘要

Single-cell chromatin accessibility sequencing (scATAC-seq) reconstructs developmental trajectory by phenotypic similarity. However, inferring the exact developmental trajectory is challenging. Previous studies showed age-associated DNA methylation (DNAm) changes in specific genomic regions, termed clock-like differential methylation loci (ClockDML). Age-associated DNAm could either result from or result in chromatin accessibility changes at ClockDML. As cells undergo mitosis, the heterogeneity of chromatin accessibility on clock-like loci is reduced, providing a measure of mitotic age. In this study, we developed a method, called EpiTrace, that counts the fraction of opened clock-like loci from scATAC-seq data... More

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