Evidence map›Paper›PMID 36163261›Full record

ArticleGenome biology2022

Single-cell multi-omics profiling links dynamic DNA methylation to cell fate decisions during mouse early organogenesis.

Stephen J Clark, Ricard Argelaguet, Tim Lohoff, Felix Krueger, Deborah Drage, Berthold Göttgens, John C Marioni, Jennifer Nichols, Wolf Reik

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. DNA methylation and cell fate in mouse embryos.Nature reviews. Genetics · 2022
    Article
  19. 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 5 institutions in 1 country.

Stephen J Clark *Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK. sclark@altoslabs.com.
Ricard Argelaguet *Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK. rargelaguet@altoslabs.com.
Tim Lohoff *Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK.
Felix KruegerAltos Labs Cambridge Institute of Science, Granta Park, Cambridge, UK.
Deborah DrageEpigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK.
Berthold GöttgensWellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge, CB2 0AW, UK.
John C MarioniCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Jennifer NicholsWellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge, CB2 0AW, UK.
Wolf ReikEpigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK. wreik@altoslabs.com.
Babraham Institute · GBCancer Research UK · GBGranta Design (United Kingdom) · GBUniversity of Cambridge · GBWellcome/MRC Cambridge Stem Cell Institute · GB

Funding

Biotechnology and Biological Sciences Research Council BBS/E/B/000C0421Medical Research Council MC_PC_17230Wellcome TrustWellcome Trust 210754/Z/18/ZWellcome Trust 220379/Z/20/Z
6 · The paper itself

Abstract

backgroundPerturbation of DNA methyltransferases (DNMTs) and of the active DNA demethylation pathway via ten-eleven translocation (TET) methylcytosine dioxygenases results in severe developmental defects and embryonic lethality. Dynamic control of DNA methylation is therefore vital for embryogenesis, yet the underlying mechanisms remain poorly understood.

resultsHere we report a single-cell transcriptomic atlas from Dnmt and Tet mutant mouse embryos during early organogenesis. We show that both the maintenance and de novo methyltransferase enzymes are dispensable for the formation of all major cell types at E8.5. However, DNA methyltransferases are required for silencing of prior or alternative cell fates such as pluripotency and extraembryonic programmes. Deletion of all three TET enzymes produces substantial lineage biases, in particular, a failure to generate primitive erythrocytes. Single-cell multi-omics profiling moreover reveals that this is linked to a failure to demethylate distal regulatory elements in Tet triple-knockout embryos.

conclusionsThis study provides a detailed analysis of the effects of perturbing DNA methylation on mouse organogenesis at a whole organism scale and affords new insights into the regulatory mechanisms of cell fate decisions.

Indexed as

DioxygenasesDNA MethylationAnimalsDNAMethyltransferasesMiceOrganogenesisDioxygenasesDNAMethyltransferases

Identifiers

PMID36163261
PMCPMC9511790
OpenAlexW4297238434

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.