Evidence map›Paper›PMID 29107594›Full record

ArticleStem cell reports2017

Genes Associated with Pancreas Development and Function Maintain Open Chromatin in iPSCs Generated from Human Pancreatic Beta Cells.

Matthias Thurner, Liraz Shenhav, Agata Wesolowska-Andersen, Amanda J Bennett, Amy Barrett, Anna L Gloyn, Mark I McCarthy, Nicola L Beer, Shimon Efrat

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

Article in Stem cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.2field-weighted citation impact, top 19% 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

7 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. 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

9 authors at 4 institutions in 2 countries.

Matthias ThurnerThe Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Liraz ShenhavDepartment of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Agata Wesolowska-AndersenThe Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Amanda J BennettOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Amy BarrettOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Anna L GloynThe Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK; Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
Mark I McCarthyThe Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK; Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
Nicola L BeerOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK. Electronic address: nicolabeer.nb@gmail.com.
Shimon EfratDepartment of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Oxford Centre for Diabetes, Endocrinology and Metabolism · GBUniversity of Oxford · GBTel Aviv University · ILCentre for Human Genetics · GB

Funding

Medical Research Council MR/L020149/1Wellcome Trust 090532Wellcome Trust 095101Wellcome Trust 098381Wellcome Trust 099673Wellcome Trust 099673/Z/12/ZWellcome Trust 1060130Wellcome Trust 200837Wellcome Trust 200837/Z/16/Z
6 · The paper itself

Abstract

Current in vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced pluripotent stem cells (iPSCs) derived from pancreatic beta cells (BiPSCs) preferentially differentiate toward endocrine pancreas-like cells versus those from fibroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq and identified ∼8.3k significant, differential open chromatin sites (DOCS) between the two iPSC subtypes (false discovery rate [FDR] < 0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR < 0.05). Bi-DOCS were associated with genes related to pancreas development and beta-cell function, including transcription factors mutated in monogenic diabetes (PDX1, NKX2-2, HNF1A; FDR < 0.05). Moreover, Bi-DOCS correlated with enhanced gene expression in BiPSC-derived definitive endoderm and pancreatic progenitor cells. Bi-DOCS therefore highlight genes and pathways governing islet-lineage commitment, which can be exploited for differentiation protocol optimization, diabetes disease modeling, and therapeutic purposes.

Indexed as

Cellular ReprogrammingGene Expression Regulation, DevelopmentalCells, CulturedChromatinEnhancer Elements, GeneticHepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 3-betaHomeobox Protein Nkx-2.2Homeodomain ProteinsHumansInduced Pluripotent Stem CellsInsulin-Secreting CellsNuclear ProteinsProtein BindingTrans-ActivatorsTranscription FactorsChromatinFOXA2 protein, humanHepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 3-betaHNF1A protein, humanHomeobox Protein Nkx-2.2Homeodomain Proteinsnkx2.2b protein, zebrafishNKX2-2 protein, humanNuclear Proteinspancreatic and duodenal homeobox 1 proteinTrans-ActivatorsTranscription FactorsZebrafish Proteinsbeta-celldiabetesendoderm differentiationepigeneticsgenomicshuman iPS cellpancreas

Identifiers

PMID29107594
PMCPMC5831005
OpenAlexW2766195602

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.