Evidence map›Paper›PMID 28636920›Full record

ArticleBiophysical journal2017

Nanog Fluctuations in Embryonic Stem Cells Highlight the Problem of Measurement in Cell Biology.

Rosanna C G Smith, Patrick S Stumpf, Sonya J Ridden, Aaron Sim, Sarah Filippi, Heather A Harrington, Ben D MacArthur

Open access · hybridAbstract read
In one paragraph

Article in Biophysical journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

9 citing papers in PubMed, 22 citations in OpenAlex.

  1. Contributions of transcriptional noise to leukaemia evolution: KAT2A as a case-study.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  2. Review
  3. Article
  4. Article
  5. Probing pluripotency gene regulatory networks with quantitative live cell imaging.Computational and structural biotechnology journal · 2020
    Review
  6. Article
  7. Review
  8. Article
  9. 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

7 authors at 3 institutions in 1 country.

Rosanna C G SmithCentre for Human Development, Stem Cells, and Regeneration, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Patrick S StumpfCentre for Human Development, Stem Cells, and Regeneration, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Sonya J RiddenMathematical Sciences, University of Southampton, Southampton, United Kingdom.
Aaron SimDepartment of Life Sciences, Imperial College London, London, United Kingdom.
Sarah FilippiDepartment of Mathematics, Imperial College London, London, United Kingdom; Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
Heather A HarringtonMathematical Institute, University of Oxford, Oxford, United Kingdom.
Ben D MacArthurCentre for Human Development, Stem Cells, and Regeneration, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Mathematical Sciences, University of Southampton, Southampton, United Kingdom; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom. Electronic address: bdm@soton.ac.uk.
University of Southampton · GBImperial College London · GBUniversity of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A number of important pluripotency regulators, including the transcription factor Nanog, are observed to fluctuate stochastically in individual embryonic stem cells. By transiently priming cells for commitment to different lineages, these fluctuations are thought to be important to the maintenance of, and exit from, pluripotency. However, because temporal changes in intracellular protein abundances cannot be measured directly in live cells, fluctuations are typically assessed using genetically engineered reporter cell lines that produce a fluorescent signal as a proxy for protein expression. Here, using a combination of mathematical modeling and experiment, we show that there are unforeseen ways in which widely used reporter strategies can systematically disturb the dynamics they are intended to monitor, sometimes giving profoundly misleading results. In the case of Nanog, we show how genetic reporters can compromise the behavior of important pluripotency-sustaining positive feedback loops, and induce a bifurcation in the underlying dynamics that gives rise to heterogeneous Nanog expression patterns in reporter cell lines that are not representative of the wild-type. These findings help explain the range of published observations of Nanog variability and highlight the problem of measurement in live cells.

Indexed as

AnimalsCell BiologyEmbryonic Stem CellsFlow CytometryGene ExpressionGene Expression RegulationGene Knock-In TechniquesGenes, ReporterGreen Fluorescent ProteinsImmunohistochemistryKineticsMaleMiceMicroscopy, FluorescenceModels, MolecularNanog Homeobox ProteinGreen Fluorescent ProteinsNanog Homeobox ProteinNanog protein, mouseRNA, Messenger

Identifiers

PMID28636920
PMCPMC5479053
OpenAlexW2681323541

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.