Evidence map›Paper›PMID 32888504›Full record

ArticleStem cell reports2020

A p53-Dependent Checkpoint Induced upon DNA Damage Alters Cell Fate during hiPSC Differentiation.

Cara B Eldridge, Finian J Allen, Alastair Crisp, Rodrigo A Grandy, Ludovic Vallier, Julian E Sale

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.3field-weighted citation impact, top 42% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

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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

6 authors at 3 institutions in 1 country.

Cara B EldridgeMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Finian J AllenDepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Alastair CrispMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Rodrigo A GrandyWellcome-MRC Cambridge Stem Cell Institute, Anne McLaren Laboratory, University of Cambridge, Cambridge CB2 0SZ, UK.
Ludovic VallierWellcome-MRC Cambridge Stem Cell Institute, Anne McLaren Laboratory, University of Cambridge, Cambridge CB2 0SZ, UK; Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UK; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1SA, UK.
Julian E SaleMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: jes@mrc-lmb.cam.ac.uk.
MRC Laboratory of Molecular Biology · GBWellcome/MRC Cambridge Stem Cell Institute · GBUniversity of Cambridge · GB

Funding

Medical Research Council G0701448Medical Research Council MC_EX_MR/S300001/1Medical Research Council MC_PC_12009Medical Research Council MC_PC_17230Medical Research Council MC_U105178808Medical Research Council U105178808National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/N001540/1National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/T2T0419Wellcome Trust
6 · The paper itself

Abstract

The ability of human induced pluripotent stem cells (hiPSCs) to differentiate in vitro to each of the three germ layer lineages has made them an important model of early human development and a tool for tissue engineering. However, the factors that disturb the intricate transcriptional choreography of differentiation remain incompletely understood. Here, we uncover a critical time window during which DNA damage significantly reduces the efficiency and fidelity with which hiPSCs differentiate to definitive endoderm. DNA damage prevents the normal reduction of p53 levels as cells pass through the epithelial-to-mesenchymal transition, diverting the transcriptional program toward mesoderm without induction of an apoptotic response. In contrast, TP53-deficient cells differentiate to endoderm with high efficiency after DNA damage, suggesting that p53 enforces a "differentiation checkpoint" in early endoderm differentiation that alters cell fate in response to DNA damage.

Indexed as

Cell Cycle CheckpointsCell DifferentiationCell LineageDNA DamageEndodermHumansInduced Pluripotent Stem CellsMesodermTranscription, GeneticTumor Suppressor Protein p53Tumor Suppressor Protein p53checkpointdefinitive endodermdifferentiationDNA-damage responsehESChiPSCp53

Identifiers

PMID32888504
PMCPMC7561492
OpenAlexW3081815394

What OpenQuestion holds

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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.