Evidence map›Paper›PMID 26406898›Full record

ArticlePloS one2015

Embryonic Stem Cell Growth Factors Regulate eIF2α Phosphorylation.

Kyle Friend, Hunter A Brooks, Nicholas E Propson, James A Thomson, Judith Kimble

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
0.3field-weighted citation impact, top 37% 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

26 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Article
  3. Overcoming the eIF2α Brake in Human Cell-Derived Translation Systems.bioRxiv : the preprint server for biology · 2025
    Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Translational control of stem cell function.Nature reviews. Molecular cell biology · 2021
    Review
  19. Ribosome heterogeneity and specialization in development.Wiley interdisciplinary reviews. RNA · 2021
    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

5 authors at 3 institutions in 1 country.

Kyle FriendDepartment of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706, United States of America; Department of Chemistry and Biochemistry, Washington and Lee University, Lexington, Virginia, 24450, United States of America.
Hunter A BrooksDepartment of Chemistry and Biochemistry, Washington and Lee University, Lexington, Virginia, 24450, United States of America.
Nicholas E PropsonThe Morgridge Institute for Research, 309 North Orchard Street, Madison, Wisconsin, 53715, United States of America.
James A ThomsonThe Morgridge Institute for Research, 309 North Orchard Street, Madison, Wisconsin, 53715, United States of America; Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, 53706, United States of America.
Judith KimbleDepartment of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706, United States of America; Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, Wisconsin, 53706, United States of America.
Morgridge Institute for Research · USWashington and Lee University · USHoward Hughes Medical Institute · US

Funding

Midwest Progenitor Cell ConsortiumU01HL099773 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI THOMSON, JAMES ALEXANDER · 2009 to 2015
$7.8M
Regulation of germline proliferation and differentiationR01GM069454 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI KIMBLE, JUDITH · 2004 to 2012
$1.8M
Howard Hughes Medical InstituteNHLBI NIH HHS 1U01 HL099773-01NHLBI NIH HHS U01 HL099773NIGMS NIH HHS GM069454NIGMS NIH HHS R01 GM069454
6 · The paper itself

Abstract

Growth factors and transcription factors are well known to regulate pluripotent stem cells, but less is known about translational control in stem cells. Here, we use embryonic stem cells (ESCs) to investigate a connection between ESC growth factors and eIF2α-mediated translational control (eIF2α phosphorylation promotes protein expression from mRNAs with upstream open-reading frames, or uORFs). We find abundant phosphorylated P-eIF2α (P-eIF2α) in both pluripotent mouse and human ESCs, but little P-eIF2α in ESCs triggered to differentiate. We show that the growth factors LIF (leukemia inhibitory factor) and BMP4 (bone morphogenic protein 4) both maintain P-eIF2α in mESCs, but use distinct mechanisms: LIF inhibits an eIF2α phosphatase whereas BMP4 activates an eIF2α kinase. The mRNAs encoding the pluripotency factors Nanog and c-Myc possess uORFs while Oct4 mRNA does not. We find that salubrinal, a chemical that increases eIF2α phosphorylation, promotes Nanog and c-Myc expression, but not Oct4 expression. These experiments connect ESC growth factors to eIF2α phosphorylation and suggest a chemical substitute for LIF to enhance Nanog and c-Myc expression.

Indexed as

AnimalsBone Morphogenetic Protein 4Cell LineCinnamatesEukaryotic Initiation Factor-2Eukaryotic Initiation Factor-4GHomeodomain ProteinsHuman Embryonic Stem CellsHumansLeukemia Inhibitory FactorMiceModels, BiologicalMouse Embryonic Stem CellsNanog Homeobox ProteinPhosphorylationProto-Oncogene Proteins c-mycBone Morphogenetic Protein 4CinnamatesEukaryotic Initiation Factor-2Eukaryotic Initiation Factor-4GHomeodomain ProteinsLeukemia Inhibitory FactorNanog Homeobox ProteinNANOG protein, humanNanog protein, mouseProto-Oncogene Proteins c-mycsalubrinalThiourea

Identifiers

PMID26406898
PMCPMC4583406
OpenAlexW2215458579

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.