Genome-wide stability of the DNA replication program in single mammalian cells
書誌事項
- 公開日
- 2019-02-25
- 資源種別
- journal article
- 権利情報
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- http://www.springer.com/tdm
- http://www.springer.com/tdm
- DOI
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- 10.1038/s41588-019-0347-5
- 10.1101/237628
- 公開者
- Springer Science and Business Media LLC
この論文をさがす
説明
<jats:title>ABSTRACT</jats:title> <jats:p> Here, we report the establishment of a <jats:underline>s</jats:underline> ingle- <jats:underline>c</jats:underline> ell DNA <jats:underline>repli</jats:underline> cation <jats:underline>seq</jats:underline> uencing method, scRepli-seq, which is a simple genome-wide methodology that measures copy number differences between replicated and unreplicated DNA. Using scRepli-seq, we demonstrate that replication domain organization is conserved among individual mouse embryonic stem cells (mESCs). Differentiated mESCs exhibited distinct replication profiles, which were conserved from cell to cell. Haplotype-resolved scRepli-seq revealed similar replication timing profiles of homologous autosomes, while the inactive X chromosome was clearly replicated later than its active counterpart. However, a small degree of cell-to-cell replication timing heterogeneity was present, and we discovered that developmentally regulated domains are a source of such variability, suggesting a link between cell-to-cell heterogeneity and developmental plasticity. Together, our results form a foundation for single-cell-level understanding of DNA replication regulation and provide insights into 3D genome organization. </jats:p>
収録刊行物
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- Nature Genetics
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Nature Genetics 51 (3), 529-540, 2019-02-25
Springer Science and Business Media LLC