Evidence map›Paper›PMID 31455402›Full record

ArticleStem cell research & therapy2019

Frequent retrotransposition of endogenous genes in ERCC2-deficient cells derived from a patient with xeroderma pigmentosum.

Saki Aoto, Saki Katagiri, Yi Wang, Alistair T Pagnamenta, Rie Sakamoto-Abutani, Masashi Toyoda, Akihiro Umezawa, Kohji Okamura

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 52% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Review
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

8 authors at 5 institutions in 3 countries.

Saki AotoMedical Genome Center, National Center for Child Health and Development Research Institute, Setagaya, Tokyo, Japan.
Saki KatagiriDepartment of Biology, Faculty of Science, Ochanomizu University, Bunkyo, Tokyo, Japan.
Yi WangMinistry of Education Key Laboratory of Contemporary Anthropology, Department of Anthropology and Human Genetics, School of Life Sciences, Fudan University, Shanghai, China.
Alistair T PagnamentaNIHR Oxford BRC, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Rie Sakamoto-AbutaniDepartment of Reproductive Biology, National Center for Child Health and Development Research Institute, Setagaya, Tokyo, Japan.
Masashi ToyodaResearch team for Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, Setagaya, Tokyo, Japan.
Akihiro UmezawaDepartment of Reproductive Biology, National Center for Child Health and Development Research Institute, Setagaya, Tokyo, Japan. umezawa@1985.jukuin.keio.ac.jp.
Kohji OkamuraDepartment of Systems BioMedicine, National Center for Child Health and Development Research Institute, Tokyo, Japan.
National Center For Child Health and Development · JPCentre for Human Genetics · GBFudan University · CNNational Institute for Basic Biology · JPTokyo Metropolitan Institute of Gerontology · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRetrotransposition of protein-coding genes is thought to occur due to the existence of numerous processed pseudogenes in both animals and plants. Unlike retrotransposons including Alu and LINE-1, direct evidence of such retrotransposition events has not been reported to date. Even if such an event occurs in a somatic cell, it is almost impossible to detect it using bulk of cells as a sample. Single-cell analyses or other techniques are needed.

methodsIn order to examine genetic stability of stem cells, we have established induced pluripotent stem cell (iPSC) lines from several patients with DNA repair-deficiency disorders, such as ataxia telangiectasia and xeroderma pigmentosum, along with healthy controls. Performing whole-exome sequencing analyses of these parental and iPSC lines, we compiled somatic mutations accumulated by the deficiency of DNA repair mechanisms. Whereas most somatic mutations cannot be detected in bulk, cell reprogramming enabled us to observe all the somatic mutations which had occurred in the cell line. Patterns of somatic mutations should be distinctive depending on which DNA repair gene is impaired.

resultsThe comparison revealed that deficiency of ATM and XPA preferentially gives rise to indels and single-nucleotide substitutions, respectively. On the other hand, deficiency of ERCC2 caused not only single-nucleotide mutations but also many retrotranspositions of endogenous genes, which were readily identified by examining removal of introns in whole-exome sequencing. Although the number was limited, those events were also detected in healthy control samples.

conclusionsThe present study exploits clonality of iPSCs to unveil somatic mutation sets that are usually hidden in bulk cell analysis. Whole-exome sequencing analysis facilitated the detection of retrotransposition mutations. The results suggest that retrotranspositions of human endogenous genes are more frequent than expected in somatic cells and that ERCC2 plays a defensive role against transposition of endogenous and exogenous DNA fragments.

Indexed as

AdultCell LineCellular ReprogrammingDNA-Binding ProteinsDNA RepairHumansInduced Pluripotent Stem CellsMaleMutationXeroderma PigmentosumXeroderma Pigmentosum Group D ProteinDNA-Binding ProteinsERCC2 protein, humanXeroderma Pigmentosum Group D ProteinDNA repairERCC2iPSCRetrotranspositionSomatic mutationXeroderma pigmentosumXPA

Identifiers

PMID31455402
PMCPMC6712803
OpenAlexW2971165226

What OpenQuestion holds

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LicenceCC BY
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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.