Evidence map›Paper›PMID 33627650›Full record

ArticleNature communications2021

Strand-specific single-cell methylomics reveals distinct modes of DNA demethylation dynamics during early mammalian development.

Maya Sen, Dylan Mooijman, Alex Chialastri, Jean-Charles Boisset, Mina Popovic, Björn Heindryckx, Susana M Chuva de Sousa Lopes, Siddharth S Dey, Alexander van Oudenaarden

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Review
  3. Macrophages in Hematopoiesis and Related Blood Diseases.Genomics, proteomics & bioinformatics · 2025
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Single-cell bisulfite-free 5mC and 5hmC sequencing with high sensitivity and scalability.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Article
  13. Article
  14. Review
  15. Cost-effective DNA methylation profiling by FML-seq.bioRxiv : the preprint server for biology · 2023
    Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 4 countries.

Maya Sen *Oncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Utrecht, The Netherlands.
Dylan Mooijman *Oncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Utrecht, The Netherlands.
Alex Chialastri *Department of Chemical Engineering, University of California Santa Barbara, Santa Barbara, CA, 93106, USA.ORCID 0000-0002-1741-8361
Jean-Charles BoissetOncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Utrecht, The Netherlands.
Mina PopovicGhent-Fertility and Stem cell Team (G-FaST), Department of Reproductive Medicine, Ghent University Hospital, 9000, Ghent, Belgium.
Björn HeindryckxGhent-Fertility and Stem cell Team (G-FaST), Department of Reproductive Medicine, Ghent University Hospital, 9000, Ghent, Belgium.ORCID 0000-0003-0630-8420
Susana M Chuva de Sousa LopesGhent-Fertility and Stem cell Team (G-FaST), Department of Reproductive Medicine, Ghent University Hospital, 9000, Ghent, Belgium.ORCID 0000-0003-3866-2803
Siddharth S DeyDepartment of Chemical Engineering, University of California Santa Barbara, Santa Barbara, CA, 93106, USA. sdey@ucsb.edu.ORCID 0000-0002-1161-1654
Alexander van OudenaardenOncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Utrecht, The Netherlands. a.vanoudenaarden@hubrecht.eu.ORCID 0000-0002-9442-3551
Royal Netherlands Academy of Arts and Sciences · NLGhent University Hospital · BEUniversity of California, Santa Barbara · USLeiden University Medical Center · NL

Funding

Understanding DNA methylation reprogramming dynamics during preimplantation development using single-cell sequencingR01HD099517 · NICHD · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI DEY, SIDDHARTH SUBHAS · 2019 to 2023
$1.4M
NICHD NIH HHS R01 HD099517
6 · The paper itself

Abstract

DNA methylation (5mC) is central to cellular identity. The global erasure of 5mC from the parental genomes during preimplantation mammalian development is critical to reset the methylome of gametes to the cells in the blastocyst. While active and passive modes of demethylation have both been suggested to play a role in this process, the relative contribution of these two mechanisms to 5mC erasure remains unclear. Here, we report a single-cell method (scMspJI-seq) that enables strand-specific quantification of 5mC, allowing us to systematically probe the dynamics of global demethylation. When applied to mouse embryonic stem cells, we identified substantial cell-to-cell strand-specific 5mC heterogeneity, with a small group of cells displaying asymmetric levels of 5mCpG between the two DNA strands of a chromosome suggesting loss of maintenance methylation. Next, in preimplantation mouse embryos, we discovered that methylation maintenance is active till the 16-cell stage followed by passive demethylation in a fraction of cells within the early blastocyst at the 32-cell stage of development. Finally, human preimplantation embryos qualitatively show temporally delayed yet similar demethylation dynamics as mouse embryos. Collectively, these results demonstrate that scMspJI-seq is a sensitive and cost-effective method to map the strand-specific genome-wide patterns of 5mC in single cells.

Indexed as

DNA DemethylationAnimalsBlastocystDNA (Cytosine-5-)-Methyltransferase 1DNA MethylationEmbryonic DevelopmentEmbryonic Stem CellsFemaleHumansMiceMice, KnockoutPregnancyDNA (Cytosine-5-)-Methyltransferase 1Dnmt1 protein, mouse

Identifiers

PMID33627650
PMCPMC7904860
OpenAlexW3132535924

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.