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

Nature Genetics
Saori TakahashiI Hiratani

Abstract

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.

References

Nov 22, 2001·Experimental Cell Research·S I TakebayashiK Okumura
Jun 1, 1960·The Journal of Biophysical and Biochemical Cytology·J H TAYLOR
May 15, 1962·Proceedings of the National Academy of Sciences of the United States of America·A MORISHIMAJ H TAYLOR
Dec 3, 2003·Human Molecular Genetics·Kathryn WoodfineNigel P Carter
Jan 10, 2006·Developmental Cell·Eran MeshorerTom Misteli
May 12, 2006·Genome Research·Alexander A Gimelbrant, Andrew Chess
Sep 29, 2006·Molecular Biology of the Cell·Ronald LebofskyAaron Bensimon
Jan 12, 2007·Development·Hitoshi Niwa
Oct 10, 2008·PLoS Biology·Ichiro HirataniDavid M Gilbert
Apr 7, 2009·Current Opinion in Genetics & Development·Ichiro HirataniDavid M Gilbert
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Dec 8, 2009·Proceedings of the National Academy of Sciences of the United States of America·R Scott HansenJohn A Stamatoyannopoulos
Jan 12, 2011·Advances in Experimental Medicine and Biology·Ichiro Hiratani, David M Gilbert
Apr 7, 2011·The EMBO Journal·Eden FussnerDavid P Bazett-Jones
Jun 4, 2011·Nature Protocols·Tyrone RybaDavid M Gilbert
Sep 17, 2011·Nature·Thomas M KeaneDavid J Adams
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium
Jul 11, 2013·Cold Spring Harbor Perspectives in Biology·Nicholas Rhind, David M Gilbert
Jul 13, 2013·Nature Protocols·Katsuhiko Hayashi, Mitinori Saitou
Oct 8, 2013·PLoS Genetics·John D CalawayFernando Pardo-Manuel de Villena
Nov 25, 2014·Cell·Amnon KorenSteven A McCarroll
Sep 12, 2015·Genome Research·Shankar P DasNicholas Rhind
Apr 27, 2016·Current Opinion in Cell Biology·Juan Carlos Rivera-Mulia, David M Gilbert
Aug 21, 2016·Genes & Development·Marie-Noëlle Prioleau, David M MacAlpine
Jan 17, 2017·Trends in Genetics : TIG·Iain C MacaulayThierry Voet
Mar 30, 2017·Genes·Shin-Ichiro TakebayashiKatsuzumi Okumura
Mar 30, 2017·Nature·Ilya M FlyamerKikuë Tachibana-Konwalski

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Citations

Sep 4, 2019·Nature Reviews. Molecular Cell Biology·Claire MarchalDavid M Gilbert
Dec 19, 2019·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Michelle L HulkeAmnon Koren
May 31, 2019·Genome Biology·Anne D Donaldson, Conrad A Nieduszynski
Mar 20, 2019·Genes·Ichiro Hiratani, Saori Takahashi
Mar 20, 2020·Biophysics Reviews·Takuya YoshizawaEiichiro Mori
Jul 28, 2020·Trends in Genetics : TIG·Patroula NathanailidouZoi Lygerou
Feb 17, 2021·Nature Communications·Britny BlumenfeldItamar Simon
May 6, 2021·International Journal of Molecular Sciences·Lina-Marie BriuJean-Charles Cadoret
Jun 3, 2021·International Journal of Molecular Sciences·Lilas CourtotValérie Bergoglio
Jul 3, 2021·Cells·Jekaterina ErenpreisaAlessandro Giuliani
Jul 15, 2021·Cell·Florencia PrattoR Daniel Camerini-Otero
Jul 29, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Caroline BrossasMarie-Noëlle Prioleau
Jan 6, 2022·Current Protocols·Daniel A BartlettDavid M Gilbert
Dec 11, 2021·Journal of Cell Science·Caitlin ConnollyShin-Ichiro Hiraga

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Datasets Mentioned

BETA
BK000964.1
DRP000194
ERP000927

Methods Mentioned

BETA
Hi-C
fluorescence-activated
immunoprecipitation
FACS
scRepli-seq
RNA-seq
single-cell Hi-C
electrophoresis
Repli-seq

Software Mentioned

AneuFinder
scRepli
Fastq
R package
MultiNA
cworld package
Picard
bwa 58
fermi
stats

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