Evidence map›Paper›PMID 26455413›Full record

ArticleStem cell reports2015

Efficient Recombinase-Mediated Cassette Exchange in hPSCs to Study the Hepatocyte Lineage Reveals AAVS1 Locus-Mediated Transgene Inhibition.

Laura Ordovás, Ruben Boon, Mariaelena Pistoni, Yemiao Chen, Esther Wolfs, Wenting Guo, Rangarajan Sambathkumar, Sylwia Bobis-Wozowicz, Nicky Helsen, Jolien Vanhove and 12 more

Erratum issuedAbstract read
In one paragraph

Article in Stem cell reports, 2015. 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 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing 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

87 citing papers in PubMed.

  1. Article
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  7. Reversing transgene silencing via targeted chromatin editing.bioRxiv : the preprint server for biology · 2025
    Article
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  11. Accelerating Diverse Cell-Based Therapies Through Scalable Design.Annual review of chemical and biomolecular engineering · 2024
    Review
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27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Laura OrdovásStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium. Electronic address: laura.ordovas@med.kuleuven.be.
Ruben BoonStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium.
Mariaelena PistoniStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium.
Yemiao ChenStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium.
Esther WolfsGroup of Morphology, Biomedical Research Institute, Hasselt University, Diepenbeek 3590, Belgium.
Wenting GuoLeuven Research Institute for Neuroscience and Disease (LIND), Leuven 3000, Belgium; Department of Neurosciences, Experimental Neurology, KU Leuven, Leuven 3000, Belgium; Laboratory for Neurobiology, VIB-Vesalius Research Center, Leuven 3000, Belgium.
Rangarajan SambathkumarStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium.
Sylwia Bobis-WozowiczInstitute for Cell and Gene Therapy, University Medical Center Freiburg, Freiburg 79108, Germany; Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg 79108, Germany.
Nicky HelsenStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium.
Jolien VanhoveStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium.
Pieter BerckmansStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium.
Qing CaiStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium.
Kim VanuytselStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium.
Kristel EggermontStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium.
Veerle VanslembrouckStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium.
Béla Z SchmidtSwitch Laboratory, VIB, Leuven 3000, Belgium; Department of Cellular and Molecular Medicine, Switch Laboratory, KU Leuven, Leuven 300, Belgium.
Susanna RaitanoStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium.
Ludo Van Den BoschLeuven Research Institute for Neuroscience and Disease (LIND), Leuven 3000, Belgium; Department of Neurosciences, Experimental Neurology, KU Leuven, Leuven 3000, Belgium; Laboratory for Neurobiology, VIB-Vesalius Research Center, Leuven 3000, Belgium.
Yaakov NahmiasDepartment of Cell and Developmental Biology, Hebrew University of Jerusalem, Jerusalem 91904, Israel; Grass Center for Bioengineering, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Toni CathomenInstitute for Cell and Gene Therapy, University Medical Center Freiburg, Freiburg 79108, Germany; Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg 79108, Germany.
Tom StruysGroup of Morphology, Biomedical Research Institute, Hasselt University, Diepenbeek 3590, Belgium.
Catherine M VerfaillieStem Cell Institute, KU Leuven, Leuven 3000, Belgium; Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, Leuven 3000, Belgium. Electronic address: catherine.verfaillie@med.kuleuven.be.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tools for rapid and efficient transgenesis in "safe harbor" loci in an isogenic context remain important to exploit the possibilities of human pluripotent stem cells (hPSCs). We created hPSC master cell lines suitable for FLPe recombinase-mediated cassette exchange (RMCE) in the AAVS1 locus that allow generation of transgenic lines within 15 days with 100% efficiency and without random integrations. Using RMCE, we successfully incorporated several transgenes useful for lineage identification, cell toxicity studies, and gene overexpression to study the hepatocyte lineage. However, we observed unexpected and variable transgene expression inhibition in vitro, due to DNA methylation and other unknown mechanisms, both in undifferentiated hESC and differentiating hepatocytes. Therefore, the AAVS1 locus cannot be considered a universally safe harbor locus for reliable transgene expression in vitro, and using it for transgenesis in hPSC will require careful assessment of the function of individual transgenes.

Indexed as

TransgenesCells, CulturedDependovirusDNA MethylationEmbryonic Stem CellsGene SilencingGene TargetingGenetic LociHepatocytesHumansInduced Pluripotent Stem CellsRecombinasesRecombinases

Identifiers

PMID26455413
PMCPMC4649136

What OpenQuestion holds

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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.