論文

査読有り 国際誌
2019年3月

Genome-wide stability of the DNA replication program in single mammalian cells.

Nature genetics
  • Saori Takahashi
  • ,
  • Hisashi Miura
  • ,
  • Takahiro Shibata
  • ,
  • Koji Nagao
  • ,
  • Katsuzumi Okumura
  • ,
  • Masato Ogata
  • ,
  • Chikashi Obuse
  • ,
  • Shin-Ichiro Takebayashi
  • ,
  • Ichiro Hiratani

51
3
開始ページ
529
終了ページ
540
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41588-019-0347-5

Here, we report a single-cell DNA replication sequencing method, scRepli-seq, a 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 profiles, which were also conserved among cells. Haplotype-resolved scRepli-seq revealed similar replication 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, which was smallest at the beginning and the end of S phase. In addition, developmentally regulated domains were found to deviate from others and showed a higher degree of heterogeneity, thus suggesting a link to developmental plasticity. Moreover, allelic expression imbalance was found to strongly associate with replication-timing asynchrony. Our results form a foundation for single-cell-level understanding of DNA replication regulation and provide insights into three-dimensional genome organization.

リンク情報
DOI
https://doi.org/10.1038/s41588-019-0347-5
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30804559
ID情報
  • DOI : 10.1038/s41588-019-0347-5
  • PubMed ID : 30804559

エクスポート
BibTeX RIS