Evidence map›Paper›PMID 26185257›Full record

ArticleStem cells translational medicine2015

Low-Dose Irradiation Enhances Gene Targeting in Human Pluripotent Stem Cells.

Seigo Hatada, Aparna Subramanian, Berhan Mandefro, Songyang Ren, Ho Won Kim, Jie Tang, Vincent Funari, Robert H Baloh, Dhruv Sareen, Vaithilingaraja Arumugaswami and 1 more

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

Article in Stem cells translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

8 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Challenges to increasing targeting efficiency in genome engineering.The Journal of reproduction and development · 2016
    Article
  6. Article
  7. Induced Pluripotent Stem Cells and Hormesis.Dose-response : a publication of International Hormesis Society
    Review
  8. Article
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

11 authors at 1 institution in 1 country.

Seigo HatadaBoard of Governors, Regenerative Medicine Institute, Department of Biomedical Sciences, iPSC Core, The David and Janet Polak Foundation Stem Cell Core Laboratory, Genomics Core Facility, Department of Surgery, and Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Aparna SubramanianBoard of Governors, Regenerative Medicine Institute, Department of Biomedical Sciences, iPSC Core, The David and Janet Polak Foundation Stem Cell Core Laboratory, Genomics Core Facility, Department of Surgery, and Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Berhan MandefroBoard of Governors, Regenerative Medicine Institute, Department of Biomedical Sciences, iPSC Core, The David and Janet Polak Foundation Stem Cell Core Laboratory, Genomics Core Facility, Department of Surgery, and Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Songyang RenBoard of Governors, Regenerative Medicine Institute, Department of Biomedical Sciences, iPSC Core, The David and Janet Polak Foundation Stem Cell Core Laboratory, Genomics Core Facility, Department of Surgery, and Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Ho Won KimBoard of Governors, Regenerative Medicine Institute, Department of Biomedical Sciences, iPSC Core, The David and Janet Polak Foundation Stem Cell Core Laboratory, Genomics Core Facility, Department of Surgery, and Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Jie TangBoard of Governors, Regenerative Medicine Institute, Department of Biomedical Sciences, iPSC Core, The David and Janet Polak Foundation Stem Cell Core Laboratory, Genomics Core Facility, Department of Surgery, and Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Vincent FunariBoard of Governors, Regenerative Medicine Institute, Department of Biomedical Sciences, iPSC Core, The David and Janet Polak Foundation Stem Cell Core Laboratory, Genomics Core Facility, Department of Surgery, and Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Robert H BalohBoard of Governors, Regenerative Medicine Institute, Department of Biomedical Sciences, iPSC Core, The David and Janet Polak Foundation Stem Cell Core Laboratory, Genomics Core Facility, Department of Surgery, and Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Dhruv SareenBoard of Governors, Regenerative Medicine Institute, Department of Biomedical Sciences, iPSC Core, The David and Janet Polak Foundation Stem Cell Core Laboratory, Genomics Core Facility, Department of Surgery, and Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Vaithilingaraja ArumugaswamiBoard of Governors, Regenerative Medicine Institute, Department of Biomedical Sciences, iPSC Core, The David and Janet Polak Foundation Stem Cell Core Laboratory, Genomics Core Facility, Department of Surgery, and Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA Clive.Svendsen@cshs.org Vaithi.Arumugaswami@cshs.org.
Clive N SvendsenBoard of Governors, Regenerative Medicine Institute, Department of Biomedical Sciences, iPSC Core, The David and Janet Polak Foundation Stem Cell Core Laboratory, Genomics Core Facility, Department of Surgery, and Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA Clive.Svendsen@cshs.org Vaithi.Arumugaswami@cshs.org.
Cedars-Sinai Medical Center · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
The Huntington's disease (HD) IPS consortiumU24NS078370 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI THOMPSON, LESLIE MICHELS · 2012 to 2013
$2.6M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NINDS NIH HHS 1U24NS078370NINDS NIH HHS U24 NS078370
6 · The paper itself

Abstract

unlabelledHuman pluripotent stem cells (hPSCs) are now being used for both disease modeling and cell therapy; however, efficient homologous recombination (HR) is often crucial to develop isogenic control or reporter lines. We showed that limited low-dose irradiation (LDI) using either γ-ray or x-ray exposure (0.4 Gy) significantly enhanced HR frequency, possibly through induction of DNA repair/recombination machinery including ataxia-telangiectasia mutated, histone H2A.X and RAD51 proteins. LDI could also increase HR efficiency by more than 30-fold when combined with the targeting tools zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats. Whole-exome sequencing confirmed that the LDI administered to hPSCs did not induce gross genomic alterations or affect cellular viability. Irradiated and targeted lines were karyotypically normal and made all differentiated lineages that continued to express green fluorescent protein targeted at the AAVS1 locus. This simple method allows higher throughput of new, targeted hPSC lines that are crucial to expand the use of disease modeling and to develop novel avenues of cell therapy. SIGNIFICANCE: The simple and relevant technique described in this report uses a low level of radiation to increase desired gene modifications in human pluripotent stem cells by an order of magnitude. This higher efficiency permits greater throughput with reduced time and cost. The low level of radiation also greatly increased the recombination frequency when combined with developed engineered nucleases. Critically, the radiation did not lead to increases in DNA mutations or to reductions in overall cellular viability. This novel technique enables not only the rapid production of disease models using human stem cells but also the possibility of treating genetically based diseases by correcting patient-derived cells.

Indexed as

Recombinational DNA RepairAtaxia Telangiectasia Mutated ProteinsCell DifferentiationCell SurvivalDeoxyribonucleasesDNA DamageExomeGamma RaysGene Expression RegulationGene TargetingGenetic LociHistonesHumansInduced Pluripotent Stem CellsInverted Repeat SequencesPluripotent Stem CellsAtaxia Telangiectasia Mutated ProteinsATM protein, humanDeoxyribonucleasesH2AX protein, humanHistonesRAD51 protein, humanRad51 RecombinaseClustered regularly interspaced short palindromic repeatsGene targetingInduced pluripotent stem cellIrradiationTranscription activator-like effector nucleaseZinc finger nuclease

Identifiers

PMID26185257
PMCPMC4542875
OpenAlexW2145726007

What OpenQuestion holds

Textmetadata
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.