Evidence map›Paper›PMID 38964325›Full record

ArticleStem cell reports2024

Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q.

Dylan Stavish, Christopher J Price, Gabriele Gelezauskaite, Haneen Alsehli, Kimberly A Leonhard, Seth M Taapken, Erik M McIntire, Owen Laing, Bethany M James, Jack J Riley and 12 more

Abstract read
In one paragraph

Article in Stem cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–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

15 citing papers in PubMed.

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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

22 authors.

Dylan StavishCentre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK.
Christopher J PriceCentre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK.
Gabriele GelezauskaiteCentre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK.
Haneen AlsehliCentre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK.
Kimberly A LeonhardWiCell Research Institute, Madison, WI, USA.
Seth M TaapkenWiCell Research Institute, Madison, WI, USA.
Erik M McIntireWiCell Research Institute, Madison, WI, USA; Department of Human Genetics, University of Chicago, Chicago, IL, USA.
Owen LaingCentre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK.
Bethany M JamesCentre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK.
Jack J RileyCentre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK.
Johanna ZerbibDepartment of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Duncan BakerSheffield Diagnostic Genetic Services, Sheffield Children's Hospital, Sheffield, UK.
Amy L HardingSchool of Clinical Dentistry, University of Sheffield, Sheffield, UK.
Lydia H JesticeCentre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK.
Thomas F EleveldPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Ad J M GillisPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Sanne HilleniusPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Leendert H J LooijengaPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Paul J GokhaleCentre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK.
Uri Ben-DavidDepartment of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Tenneille E LudwigWiCell Research Institute, Madison, WI, USA; Office of the Vice Chancellor for Research and Graduate Education, University of Wisconsin-Madison, Madison, WI, USA.
Ivana BarbaricCentre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield, UK; Neuroscience Institute, The University of Sheffield, Sheffield, UK; INSIGNEO Institute, The University of Sheffield, Sheffield, UK. Electronic address: i.barbaric@sheffield.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Culture-acquired variants in human pluripotent stem cells (hPSCs) hinder their applications in research and clinic. However, the mechanisms that underpin selection of variants remain unclear. Here, through analysis of comprehensive karyotyping datasets from over 23,000 hPSC cultures of more than 1,500 lines, we explored how culture conditions shape variant selection. Strikingly, we identified an association of chromosome 1q gains with feeder-free cultures and noted a rise in its prevalence in recent years, coinciding with increased usage of feeder-free regimens. Competition experiments of multiple isogenic lines with and without a chromosome 1q gain confirmed that 1q variants have an advantage in feeder-free (E8/vitronectin), but not feeder-based, culture. Mechanistically, we show that overexpression of MDM4, located on chromosome 1q, drives variants' advantage in E8/vitronectin by alleviating genome damage-induced apoptosis, which is lower in feeder-based conditions. Our study explains condition-dependent patterns of hPSC aberrations and offers insights into the mechanisms of variant selection.

Indexed as

Chromosomes, Human, Pair 1Pluripotent Stem CellsApoptosisCell Culture TechniquesCell Cycle ProteinsCell LineCells, CulturedFeeder CellsHumansProto-Oncogene ProteinsCell Cycle ProteinsMDM4 protein, humanProto-Oncogene Proteinsculture conditionsgenetic changesgenome damagehuman pluripotent stem cellsMDM4

Identifiers

PMID38964325
PMCPMC11368687

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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.