Evidence map›Paper›PMID 31185456›Full record

ArticleiScience2019

Multiomics Analyses of HNF4α Protein Domain Function during Human Pluripotent Stem Cell Differentiation.

Yu Wang, Michael H Tatham, Wolfgang Schmidt-Heck, Carolyn Swann, Karamjit Singh-Dolt, Jose Meseguer-Ripolles, Baltasar Lucendo-Villarin, Tilo Kunath, Timothy R Rudd, Andrew J H Smith and 4 more

Abstract read
In one paragraph

Article in iScience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Yu WangMedical Research Council Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, Scotland EH16 4UU, UK.
Michael H TathamCentre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Wolfgang Schmidt-HeckLeibniz Institute for Natural Product Research and Infection Biology eV-Hans-Knoll Institute, Jena, Germany.
Carolyn SwannNational Institute for Biological Standards and Control (MHRA), Blanche Lane, South Mimms, Hertfordshire EN6 3QG, UK.
Karamjit Singh-DoltMedical Research Council Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, Scotland EH16 4UU, UK.
Jose Meseguer-RipollesMedical Research Council Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, Scotland EH16 4UU, UK.
Baltasar Lucendo-VillarinMedical Research Council Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, Scotland EH16 4UU, UK.
Tilo KunathMedical Research Council Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, Scotland EH16 4UU, UK.
Timothy R RuddNational Institute for Biological Standards and Control (MHRA), Blanche Lane, South Mimms, Hertfordshire EN6 3QG, UK.
Andrew J H SmithMedical Research Council Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, Scotland EH16 4UU, UK.
Jan G HengstlerIfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
Patricio GodoyIfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
Ronald T HayCentre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
David C HayMedical Research Council Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, Scotland EH16 4UU, UK. Electronic address: davehay@talktalk.net.

Funding

Cancer Research UK 21747Chief Scientist Office TCS/16/37Medical Research Council MC_UU_00016/10Wellcome Trust
6 · The paper itself

Abstract

During mammalian development, liver differentiation is driven by signals that converge on multiple transcription factor networks. The hepatocyte nuclear factor signaling network is known to be essential for hepatocyte specification and maintenance. In this study, we have generated deletion and point mutants of hepatocyte nuclear factor-4alpha (HNF4α) to precisely evaluate the function of protein domains during hepatocyte specification from human pluripotent stem cells. We demonstrate that nuclear HNF4α is essential for hepatic progenitor specification, and the introduction of point mutations in HNF4α's Small Ubiquitin-like Modifier (SUMO) consensus motif leads to disrupted hepatocyte differentiation. Taking a multiomics approach, we identified key deficiencies in cell biology, which included dysfunctional metabolism, substrate adhesion, tricarboxylic acid cycle flux, microRNA transport, and mRNA processing. In summary, the combination of genome editing and multiomics analyses has provided valuable insight into the diverse functions of HNF4α during pluripotent stem cell entry into the hepatic lineage and during hepatocellular differentiation.

Indexed as

Biological SciencesCell BiologyDevelopmental BiologyStem Cells Research

Identifiers

PMID31185456
PMCPMC6556878

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.