Evidence map›Paper›PMID 26946228›Full record

ArticleStem cells (Dayton, Ohio)2016

Lineage-Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause.

Jennifer J Van Oudenhove, Rodrigo A Grandy, Prachi N Ghule, Roxana Del Rio, Jane B Lian, Janet L Stein, Sayyed K Zaidi, Gary S Stein

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Embryonic Stem Cell-Specific Responses to DNA Replication Stress.bioRxiv : the preprint server for biology · 2025
    Article
  3. Article
  4. Imaging developmental cell cycles.Biophysical journal · 2021
    Review
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  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Jennifer J Van OudenhoveDepartment of Biochemistry and University of Vermont Cancer Center, Burlington, VT, USA.
Rodrigo A GrandyDepartment of Biochemistry and University of Vermont Cancer Center, Burlington, VT, USA.
Prachi N GhuleDepartment of Biochemistry and University of Vermont Cancer Center, Burlington, VT, USA.
Roxana Del RioDepartment of Surgery and Flow Cytometry & Cell Sorting Facility, University of Vermont College of Medicine, Burlington, VT, USA.
Jane B LianDepartment of Biochemistry and University of Vermont Cancer Center, Burlington, VT, USA.
Janet L SteinDepartment of Biochemistry and University of Vermont Cancer Center, Burlington, VT, USA.
Sayyed K ZaidiDepartment of Biochemistry and University of Vermont Cancer Center, Burlington, VT, USA.
Gary S SteinDepartment of Biochemistry and University of Vermont Cancer Center, Burlington, VT, USA.
University of Vermont · US

Funding

Vermont INBRE Administrative Supplement 2024 AWD 118P20GM103449 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI CHRISTOPHER S FRANCKLYN · 2012 to 2026
$58.4M
SUBNUCLEAR TARGETING OF TRANSCRIPTION FACTORSP01CA082834 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI STEIN, GARY S. · 2001 to 2015
$18.4M
Cell Cycle Regulation of Histone Gene ExpressionR01CA139322 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI STEIN, GARY S. · 2009 to 2013
$1.6M
Upgrade of a FACS Aria Cell SorterS10OD018175 · OD · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI BOYSON, JONATHAN E · 2015 to 2015
$153k
NCI NIH HHS P01 CA082834NCI NIH HHS R01 CA139322NIGMS NIH HHS P20 GM103449NIH HHS S10 OD018175
6 · The paper itself

Abstract

Human embryonic stem cells (hESCs) have an abbreviated G1 phase of the cell cycle that allows rapid proliferation and maintenance of pluripotency. Lengthening of G1 corresponds to loss of pluripotency during differentiation. However, precise mechanisms that link alterations in the cell cycle and early differentiation remain to be defined. We investigated initial stages of mesendodermal lineage commitment in hESCs, and observed a cell cycle pause. Transcriptome profiling identified several genes with known roles in regulation of the G2/M transition that were differentially expressed early during lineage commitment. WEE1 kinase, which blocks entry into mitosis by phosphorylating CDK1 at Y15, was the most highly expressed of these genes. Inhibition of CDK1 phosphorylation by a specific inhibitor of WEE1 restored cell cycle progression by preventing the G2 pause. Directed differentiation of hESCs revealed that cells paused during commitment to the endo- and mesodermal, but not ectodermal, lineages. Functionally, WEE1 inhibition during meso- and endodermal differentiation selectively decreased expression of definitive endodermal markers SOX17 and FOXA2. Our findings identify a novel G2 cell cycle pause that is required for endodermal differentiation and provide important new mechanistic insights into early events of lineage commitment. Stem Cells 2016;34:1765-1775.

Indexed as

Cell Cycle CheckpointsCell DifferentiationCell LineageG2 PhaseCDC2 Protein KinaseCell Cycle ProteinsCluster AnalysisEmbryonic Stem CellsEndodermFemaleGene Expression ProfilingHumansMaleMesodermModels, BiologicalNuclear ProteinsCDC2 Protein KinaseCell Cycle ProteinsNuclear ProteinsProtein-Tyrosine KinasesWEE1 protein, humanCDC2 protein kinaseCell cycleCell differentiationEmbryonic stem cellsEndoderm

Identifiers

PMID26946228
PMCPMC4931987
OpenAlexW2291248468

What OpenQuestion holds

Textmetadata
LicenceTDM
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.