Evidence map›Paper›PMID 32427826›Full record

ArticleNature communications2020

The mutational impact of culturing human pluripotent and adult stem cells.

Ewart Kuijk, Myrthe Jager, Bastiaan van der Roest, Mauro D Locati, Arne Van Hoeck, Jerome Korzelius, Roel Janssen, Nicolle Besselink, Sander Boymans, Ruben van Boxtel and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. 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 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
6.3field-weighted citation impact, top 2% 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

76 citing papers in PubMed, 118 citations in OpenAlex.

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  16. Single-cell cloning and its approaches.Frontiers in cell and developmental biology · 2025
    Review
  17. Culture-acquired genetic variation in human pluripotent stem cells: Twenty years on.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024
    Review
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Ewart KuijkCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands. E.W.Kuijk-3@umcutrecht.nl.ORCID http://orcid.org/0000-0002-1385-6516
Myrthe JagerCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-1406-1715
Bastiaan van der RoestCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-8985-8964
Mauro D LocatiCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
Arne Van HoeckCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-6570-1452
Jerome KorzeliusLeibniz Institute on Aging-Fritz Lipmann Institute, Beutenbergstraße 11, Jena, 07745, Germany.ORCID http://orcid.org/0000-0002-8443-0192
Roel JanssenCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0003-4324-5350
Nicolle BesselinkCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-8961-4441
Sander BoymansCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-3517-2684
Ruben van BoxtelPrincess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0003-1285-2836
Edwin CuppenCenter for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands. ecuppen@umcutrecht.nl.ORCID http://orcid.org/0000-0002-0400-9542
University Medical Center Utrecht · NLLeibniz Institute on Aging - Fritz Lipmann Institute (FLI) · DEPrincess Máxima Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Genetic changes acquired during in vitro culture pose a risk for the successful application of stem cells in regenerative medicine. To assess the genetic risks induced by culturing, we determined all mutations in individual human stem cells by whole genome sequencing. Individual pluripotent, intestinal, and liver stem cells accumulate 3.5 ± 0.5, 7.2 ± 1.1 and 8.3 ± 3.6 base substitutions per population doubling, respectively. The annual in vitro mutation accumulation rate of adult stem cells is nearly 40-fold higher than the in vivo mutation accumulation rate. Mutational signature analysis reveals that in vitro induced mutations are caused by oxidative stress. Reducing oxygen tension in culture lowers the mutational load. We use the mutation rates, spectra, and genomic distribution to model the accumulation of oncogenic mutations during typical in vitro expansion, manipulation or screening experiments using human stem cells. Our study provides empirically defined parameters to assess the mutational risk of stem cell based therapies.

Indexed as

MutationAdultAdult Stem CellsAlgorithmsCells, CulturedDNA Mutational AnalysisHumansInduced Pluripotent Stem CellsIntestinesLiverModels, GeneticMutation AccumulationMutation RateRegenerative MedicineWhole Genome Sequencing

Identifiers

PMID32427826
PMCPMC7237696
OpenAlexW3028024776

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.