Evidence map›Paper›PMID 26771352›Full record

ArticleStem cell reports2016

Overcoming Pluripotent Stem Cell Dependence on the Repair of Endogenous DNA Damage.

Timothy M Chlon, Sonya Ruiz-Torres, Logan Maag, Christopher N Mayhew, Kathryn A Wikenheiser-Brokamp, Stella M Davies, Parinda Mehta, Kasiani C Myers, James M Wells, Susanne I Wells

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

19 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Transcription-replication conflicts in primordial germ cells necessitate the Fanconi anemia pathway to safeguard genome stability.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  6. Review
  7. Article
  8. Article
  9. DNA repair fidelity in stem cell maintenance, health, and disease.Biochimica et biophysica acta. Molecular basis of disease · 2020
    Review
  10. Article
  11. Article
  12. Article
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  15. Review
  16. Review
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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

10 authors at 1 institution in 1 country.

Timothy M ChlonCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC-7013, Cincinnati, OH 45229, USA.
Sonya Ruiz-TorresCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC-7013, Cincinnati, OH 45229, USA.
Logan MaagCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC-7013, Cincinnati, OH 45229, USA.
Christopher N MayhewDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Kathryn A Wikenheiser-BrokampDivisions of Pathology and Laboratory Medicine and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45220, USA.
Stella M DaviesCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC-7013, Cincinnati, OH 45229, USA.
Parinda MehtaCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC-7013, Cincinnati, OH 45229, USA.
Kasiani C MyersCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC-7013, Cincinnati, OH 45229, USA.
James M WellsDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Susanne I WellsCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC-7013, Cincinnati, OH 45229, USA. Electronic address: susanne.wells@cchmc.org.
Cincinnati Children's Hospital Medical Center · US

Funding

LCenter for Clinical and Translational Science and TrainingUL1TR001425 · NCATS · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E., KISSELA, BRETT M · 2015 to 2024
$37.5M
Pediatric Center--Gene Expression /Developmental ScienceK12HD028827 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI Tina Lee Cheng · 2002 to 2026
$9.6M
Training Program in Cancer TherapeuticsT32CA117846 · NCI · UNIVERSITY OF CINCINNATI · PI PRICE, CAROLYN M, TAKIAR, VINITA · 2006 to 2022
$6.5M
Papillomavirus Proteins Mediating Cancer and SenescenceR01CA102357 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI WELLS, SUSANNE I · 2004 to 2013
$2.6M
NCATS NIH HHS UL1 TR001425NCI NIH HHS R01 CA102357NCI NIH HHS T32 CA117846NICHD NIH HHS K12 HD028827
6 · The paper itself

Abstract

Pluripotent stem cells (PSCs) maintain a low mutation frequency compared with somatic cell types at least in part by preferentially utilizing error-free homologous recombination (HR) for DNA repair. Many endogenous metabolites cause DNA interstrand crosslinks, which are repaired by the Fanconi anemia (FA) pathway using HR. To determine the effect of failed repair of endogenous DNA lesions on PSC biology, we generated iPSCs harboring a conditional FA pathway. Upon FA pathway loss, iPSCs maintained pluripotency but underwent profound G2 arrest and apoptosis, whereas parental fibroblasts grew normally. Mechanistic studies revealed that G2-phase FA-deficient iPSCs possess large γH2AX-RAD51 foci indicative of accrued DNA damage, which correlated with activated DNA-damage signaling through CHK1. CHK1 inhibition specifically rescued the growth of FA-deficient iPSCs for prolonged culture periods, surprisingly without stimulating excessive karyotypic abnormalities. These studies reveal that PSCs possess hyperactive CHK1 signaling that restricts their self-renewal in the absence of error-free DNA repair.

Indexed as

DNA DamageDNA RepairApoptosisBlotting, WesternCells, CulturedCheckpoint Kinase 1Fanconi AnemiaFanconi Anemia Complementation Group ProteinsFibroblastsG2 Phase Cell Cycle CheckpointsHistonesHomologous RecombinationHumansInduced Pluripotent Stem CellsPluripotent Stem CellsProtein KinasesCheckpoint Kinase 1CHEK1 protein, humanFanconi Anemia Complementation Group ProteinsH2AX protein, humanHistonesProtein KinasesRad51 Recombinase

Identifiers

PMID26771352
PMCPMC4719133
OpenAlexW2238365735

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.