Evidence map›Paper›PMID 24901476›Full record

ArticlePLoS genetics2014

Genetic background drives transcriptional variation in human induced pluripotent stem cells.

Foad Rouhani, Natsuhiko Kumasaka, Miguel Cardoso de Brito, Allan Bradley, Ludovic Vallier, Daniel Gaffney

Abstract read
In one paragraph

Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
187citing papers in PubMed, 1 pooled it
–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

187 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Advances in Microfluidic Cochlea-On-A-Chip.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  11. Article
  12. Article
  13. Pluripotent cell states and fates in human embryo models.Development (Cambridge, England) · 2025
    Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. A Novel Stem Cell Model to Study Preeclampsia Endothelial Dysfunction.Reproductive sciences (Thousand Oaks, Calif.) · 2024
    Article
  19. Review
  20. Article

127 more citing papers are in PubMed but not listed here.

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

6 authors.

Foad RouhaniWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Natsuhiko KumasakaWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Miguel Cardoso de BritoUniversity of Cambridge, Cambridge, Cambridge, United Kingdom.
Allan BradleyWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Ludovic VallierWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom; University of Cambridge, Cambridge, Cambridge, United Kingdom.
Daniel GaffneyWellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.

Funding

Wellcome TrustWellcome Trust 098051
6 · The paper itself

Abstract

Human iPS cells have been generated using a diverse range of tissues from a variety of donors using different reprogramming vectors. However, these cell lines are heterogeneous, which presents a limitation for their use in disease modeling and personalized medicine. To explore the basis of this heterogeneity we generated 25 iPS cell lines under normalised conditions from the same set of somatic tissues across a number of donors. RNA-seq data sets from each cell line were compared to identify the majority contributors to transcriptional heterogeneity. We found that genetic differences between individual donors were the major cause of transcriptional variation between lines. In contrast, residual signatures from the somatic cell of origin, so called epigenetic memory, contributed relatively little to transcriptional variation. Thus, underlying genetic background variation is responsible for most heterogeneity between human iPS cell lines. We conclude that epigenetic effects in hIPSCs are minimal, and that hIPSCs are a stable, robust and powerful platform for large-scale studies of the function of genetic differences between individuals. Our data also suggest that future studies using hIPSCs as a model system should focus most effort on collection of large numbers of donors, rather than generating large numbers of lines from the same donor.

Indexed as

AdultBase SequenceCell DifferentiationCells, CulturedEmbryonic Stem CellsEndothelial CellsEpigenomicsFemaleFibroblastsHumansInduced Pluripotent Stem CellsKeratinocytesMaleSequence AlignmentSequence Analysis, RNATranscription, Genetic

Identifiers

PMID24901476
PMCPMC4046971

What OpenQuestion holds

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Read underepoch 390

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.