Evidence map›Paper›PMID 29779897›Full record

ArticleStem cell reports2018

Inductive and Selective Effects of GSK3 and MEK Inhibition on Nanog Heterogeneity in Embryonic Stem Cells.

Simon Hastreiter, Stavroula Skylaki, Dirk Loeffler, Andreas Reimann, Oliver Hilsenbeck, Philipp S Hoppe, Daniel L Coutu, Konstantinos D Kokkaliaris, Michael Schwarzfischer, Konstantinos Anastassiadis and 2 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 23% 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, 32 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. 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

12 authors at 4 institutions in 2 countries.

Simon HastreiterDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland; Research Unit Stem Cell Dynamics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Stavroula SkylakiDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland; Research Unit Stem Cell Dynamics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Dirk LoefflerDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland; Research Unit Stem Cell Dynamics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Andreas ReimannDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland.
Oliver HilsenbeckDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland; Research Unit Stem Cell Dynamics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Philipp S HoppeDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland; Research Unit Stem Cell Dynamics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Daniel L CoutuDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland; Research Unit Stem Cell Dynamics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Konstantinos D KokkaliarisDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland; Research Unit Stem Cell Dynamics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Michael SchwarzfischerInstitute of Computational Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
Konstantinos AnastassiadisStem Cell Engineering, Biotechnology Center, Technische Universität Dresden, 01307 Dresden, Germany.
Fabian J TheisInstitute of Computational Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Department of Mathematics, Technische Universität München, 85748 Garching, Germany.
Timm SchroederDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland; Research Unit Stem Cell Dynamics, Helmholtz Zentrum München, 85764 Neuherberg, Germany. Electronic address: timm.schroeder@bsse.ethz.ch.
ETH Zurich · CHHelmholtz Zentrum München · DETechnical University of Munich · DETU Dresden · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Embryonic stem cells (ESCs) display heterogeneous expression of pluripotency factors such as Nanog when cultured with serum and leukemia inhibitory factor (LIF). In contrast, dual inhibition of the signaling kinases GSK3 and MEK (2i) converts ESC cultures into a state with more uniform and high Nanog expression. However, it is so far unclear whether 2i acts through an inductive or selective mechanism. Here, we use continuous time-lapse imaging to quantify the dynamics of death, proliferation, and Nanog expression in mouse ESCs after 2i addition. We show that 2i has a dual effect: it both leads to increased cell death of Nanog low ESCs (selective effect) and induces and maintains high Nanog levels (inductive effect) in single ESCs. Genetic manipulation further showed that presence of NANOG protein is important for cell viability in 2i medium. This demonstrates complex Nanog-dependent effects of 2i treatment on ESC cultures.

Indexed as

AnimalsCell DifferentiationCell LineEmbryonic Stem CellsGene ExpressionGene Knockout TechniquesGlycogen Synthase Kinase 3MAP Kinase Kinase 2MiceNanog Homeobox ProteinProtein Kinase InhibitorsSignal TransductionSingle-Cell AnalysisGlycogen Synthase Kinase 3MAP Kinase Kinase 2Nanog Homeobox ProteinProtein Kinase Inhibitors2icell fatecell heterogeneitycontinuous time-lapse imagingembryonic stem cellsGsk3MekNanogpluripotencysingle-cell tracking

Identifiers

PMID29779897
PMCPMC6066909
OpenAlexW2803353986

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.