Evidence map›Paper›PMID 26812582›Full record

ArticlePLoS genetics2016

Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs.

Courtney K Burrows, Nicholas E Banovich, Bryan J Pavlovic, Kristen Patterson, Irene Gallego Romero, Jonathan K Pritchard, Yoav Gilad

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 1 pooled it
9.9field-weighted citation impact, top 2% 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

90 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.

  1. Pooled it
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  18. ICF1-Syndrome-AssociatedBiomolecules · 2023
    Article
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30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Courtney K BurrowsDepartment of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.
Nicholas E BanovichDepartment of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.
Bryan J PavlovicDepartment of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.
Kristen PattersonDepartment of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.
Irene Gallego RomeroDepartment of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.
Jonathan K PritchardHoward Hughes Medical Institute, Stanford University, Stanford, California, United States of America.
Yoav GiladDepartment of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.
University of Chicago · USStanford University · US

Funding

PREDOCTORAL TRAINING IN GENETICS AND REGULATIONT32GM007197 · NIGMS · UNIVERSITY OF CHICAGO · PI ROTHMAN-DENES, LUCIA B. B · 1985 to 2020
$17.0M
Integrating genomics and gene expression analyses to map CVD-associated lociR01HL092206 · NHLBI · UNIVERSITY OF CHICAGO · PI GILAD, YOAV · 2009 to 2021
$7.3M
Analysis and interpretation of noncoding regulatory variationR01MH084703 · NIMH · UNIVERSITY OF CHICAGO · PI GILAD, YOAV, PRITCHARD, JONATHAN K · 2008 to 2015
$3.4M
Mapping QTLs Associated with Variation in RNA Decay RatesR01HG006123 · NHGRI · UNIVERSITY OF CHICAGO · PI GILAD, YOAV · 2011 to 2013
$1.3M
Genetic Factors Governing Inter-individual Variation to Oxidative Stress ResponseF31AG044948 · NIA · UNIVERSITY OF CHICAGO · PI BANOVICH, NICHOLAS ELI · 2013 to 2016
$119k
Howard Hughes Medical InstituteNHGRI NIH HHS HG006123NHGRI NIH HHS R01 HG006123NHLBI NIH HHS R01 HL092206NIA NIH HHS F31 AG 044948NIA NIH HHS F31 AG044948NIGMS NIH HHS GM007197NIGMS NIH HHS T32 GM007197NIMH NIH HHS MH084703NIMH NIH HHS R01 MH084703Wellcome Trust
6 · The paper itself

Abstract

The advent of induced pluripotent stem cells (iPSCs) revolutionized human genetics by allowing us to generate pluripotent cells from easily accessible somatic tissues. This technology can have immense implications for regenerative medicine, but iPSCs also represent a paradigm shift in the study of complex human phenotypes, including gene regulation and disease. Yet, an unresolved caveat of the iPSC model system is the extent to which reprogrammed iPSCs retain residual phenotypes from their precursor somatic cells. To directly address this issue, we used an effective study design to compare regulatory phenotypes between iPSCs derived from two types of commonly used somatic precursor cells. We find a remarkably small number of differences in DNA methylation and gene expression levels between iPSCs derived from different somatic precursors. Instead, we demonstrate genetic variation is associated with the majority of identifiable variation in DNA methylation and gene expression levels. We show that the cell type of origin only minimally affects gene expression levels and DNA methylation in iPSCs, and that genetic variation is the main driver of regulatory differences between iPSCs of different donors. Our findings suggest that studies using iPSCs should focus on additional individuals rather than clones from the same individual.

Indexed as

EpigenomicsInduced Pluripotent Stem CellsCell DifferentiationCell LineageDNA MethylationFibroblastsGene Expression Regulation, DevelopmentalGenetic VariationHumans

Identifiers

PMID26812582
PMCPMC4727884
OpenAlexW2263947150

What OpenQuestion holds

Textmetadata
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.