Evidence map›Paper›PMID 25646475›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Haploinsufficiency screen highlights two distinct groups of ribosomal protein genes essential for embryonic stem cell fate.

Simon Fortier, Tara MacRae, Mélanie Bilodeau, Tobias Sargeant, Guy Sauvageau

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
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

20 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
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  7. Article
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  9. Article
  10. Translational control of stem cell function.Nature reviews. Molecular cell biology · 2021
    Review
  11. Article
  12. Article
  13. Review
  14. Ribosome Stoichiometry: From Form to Function.Trends in biochemical sciences · 2019
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  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

5 authors.

Simon FortierMolecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, H3C 3J7, Canada;
Tara MacRaeMolecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, H3C 3J7, Canada;
Mélanie BilodeauMolecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, H3C 3J7, Canada;
Tobias SargeantMolecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, H3C 3J7, Canada; Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3050, Australia; and Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
Guy SauvageauMolecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, QC, H3C 3J7, Canada; guy.sauvageau@umontreal.ca.

Funding

Canadian Institutes of Health Research MOP 82814
6 · The paper itself

Abstract

In a functional genomics screen of mouse embryonic stem cells (ESCs) with nested hemizygous chromosomal deletions, we reveal that ribosomal protein (RP) genes are the most significant haploinsufficient determinants for embryoid body (EB) formation. Hemizygocity for three RP genes (Rps5, Rps14, or Rps28), distinguished by the proximity of their corresponding protein to the ribosome's mRNA exit site, is associated with the most profound phenotype. This EB phenotype was fully rescued by BAC or cDNA complementation but not by the reduction of p53 levels, although such reduction was effective with most other RP-deleted clones corresponding to non-mRNA exit-site proteins. RNA-sequencing studies further revealed that undifferentiated ESCs hemizygous for Rps5 showed reduced expression levels of several mesoderm-specific genes as compared with wild-type counterparts. Together, these results reveal that RP gene dosage limits the differentiation, not the self-renewal, of mouse ESCs. They also highlight two separate mechanisms underlying this process, one of which is p53 independent.

Indexed as

Cell LineageHaploinsufficiencyAnimalsCell LineEmbryonic Stem CellsHumansMaleMiceRibosomal ProteinsTumor Suppressor Protein p53Ribosomal ProteinsTP53 protein, humanTumor Suppressor Protein p53differentiationembryoid bodyembryonic stem cellsribosomal proteins

Identifiers

PMID25646475
PMCPMC4343140

What OpenQuestion holds

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Registered trials

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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.