Evidence map›Paper›PMID 32442913›Full record

ArticleStem cell research2020

Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program.

Kanika Kanchan, Kruthika Iyer, Lisa R Yanek, Ivan Carcamo-Orive, Margaret A Taub, Claire Malley, Kristin Baldwin, Lewis C Becker, Ulrich Broeckel, Linzhao Cheng and 15 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 33% 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

6 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

25 authors at 11 institutions in 1 country.

Kanika KanchanDepartment of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Kruthika IyerDepartment of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Lisa R YanekDepartment of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Ivan Carcamo-OriveDepartment of Medicine, Cardiovascular Institute and Diabetes Research Center, Stanford University, School of Medicine, Stanford, CA, USA.
Margaret A TaubDepartment of Biostatistics, Bloomberg School of Public health, Johns Hopkins University, Baltimore, MD, USA.
Claire MalleyDepartment of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Kristin BaldwinDepartment of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA.
Lewis C BeckerDepartment of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Ulrich BroeckelDepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
Linzhao ChengDepartment of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Chad CowanDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Matteo D'AntonioInstitute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Kelly A FrazerInstitute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Thomas QuertermousDepartment of Medicine, Cardiovascular Institute and Diabetes Research Center, Stanford University, School of Medicine, Stanford, CA, USA.
Gustavo MostoslavskyThe Center for Regenerative Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
George MurphyThe Center for Regenerative Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
Marlene RabinovitchDepartment of Medicine, Cardiovascular Institute and Diabetes Research Center, Stanford University, School of Medicine, Stanford, CA, USA.
Daniel J RaderDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Martin H SteinbergDepartment of Medicine, Section of Hematology-Oncology, Boston University School of Medicine, Boston, MA, USA.
Eric TopolDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Wenli YangPenn Center for Pulmonary Biology and Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Joshua W KnowlesDepartment of Medicine, Cardiovascular Institute and Diabetes Research Center, Stanford University, School of Medicine, Stanford, CA, USA.
Cashell E JaquishNational Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
Ingo RuczinskiDepartment of Biostatistics, Bloomberg School of Public health, Johns Hopkins University, Baltimore, MD, USA.
Rasika A MathiasDepartment of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Johns Hopkins University · USJohns Hopkins Medicine · USStanford University · USBoston Medical Center · USScripps Research Institute · USUniversity of California, San Diego · USUniversity of Pennsylvania · USBeth Israel Deaconess Medical Center · USBoston University · USMedical College of Wisconsin · USNational Heart Lung and Blood Institute · US

Funding

Stanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Seung K Kim · 2017 to 2026
$19.5M
Genotypic Determinants of Aspirin Response in High Risk FamiliesU01HL072518 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI BECKER, LEWIS C · 2002 to 2008
$12.8M
REGULATORY GENOMIC STUDIES IN A COHORT OF IPS CELL DERIVED CARDIOMYOCYTESU01HL107442 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EVANS, SYLVIA M, FRAZER, KELLY A · 2011 to 2016
$9.8M
Integrating lipid genotyes and phenotypes in iPS derived hepatocytes/adipocytesU01HL107440 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI COWAN, CHAD ALBERT, DEO, RAHUL CHANDRAKANT · 2011 to 2015
$9.0M
Functional Genomics of Platelet Aggregation Using iPS and Derived MegakaryocytesU01HL107446 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI BECKER, LEWIS C, CHENG, LINZHAO · 2011 to 2015
$8.8M
Identifying the gene networks of insulin resistance: the GENESIPS studyU01HL107388 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS, SCHADT, ERIC E · 2011 to 2015
$8.8M
iPSC Derived EC as Surrogates Using Pulmonary Hypertension as a Prototype DiseaseU01HL107393 · NHLBI · STANFORD UNIVERSITY · PI RABINOVITCH, MARLENE, SNYDER, MICHAEL P. · 2011 to 2015
$8.7M
iPS-derived hepatocytes for interrogation of lipid phenotypesU01HG006398 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI RADER, DANIEL JAMES · 2011 to 2015
$8.6M
Globin Gene Expression in Sickle Cell Genotype-Specific iPS cellsU01HL107443 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI CHUI, DAVID H K, MOSTOSLAVSKY, GUSTAVO · 2011 to 2015
$8.3M
Elucidating cardiovascular phenotaypes employing genome editing of iPS cellsU01HL107436 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI BALDWIN, KRISTIN KAY, TOPOL, ERIC JEFFREY · 2011 to 2015
$7.7M
The BMP-PPARy Axis and Pulmonary HypertensionR01HL087118 · NHLBI · STANFORD UNIVERSITY · PI RABINOVITCH, MARLENE · 2008 to 2022
$7.2M
Defining a transcriptional periodic table of the human brain using reprogrammingDP1AG055944 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI BALDWIN, KRISTIN KAY · 2016 to 2020
$7.2M
NHGRI NIH HHS U01 HG006398NHLBI NIH HHS HHSN268201100037CNHLBI NIH HHS R01 HL087118NHLBI NIH HHS R01 HL112064NHLBI NIH HHS U01 HL072518NHLBI NIH HHS U01 HL107388NHLBI NIH HHS U01 HL107393NHLBI NIH HHS U01 HL107436NHLBI NIH HHS U01 HL107437NHLBI NIH HHS U01 HL107440NHLBI NIH HHS U01 HL107442NHLBI NIH HHS U01 HL107443NHLBI NIH HHS U01 HL107446NIA NIH HHS DP1 AG055944NIA NIH HHS R56 AG062618NIDDK NIH HHS P30 DK116074NIDDK NIH HHS R01 DK106236NIDDK NIH HHS R01 DK116750NIMH NIH HHS R01 MH102698
6 · The paper itself

Abstract

Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models.

Indexed as

Induced Pluripotent Stem CellsCell DifferentiationDNA-Binding ProteinsDNA Copy Number VariationsGenomic InstabilityGenomicsHumansNational Heart, Lung, and Blood Institute (U.S.)United StatesDNA-Binding ProteinsPDRG1 protein, humanGWAS, VanillaICEhiPSCsOncogenesStructural integrityTumor suppressor genes

Identifiers

PMID32442913
PMCPMC7575060
OpenAlexW3022113968

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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.