Evidence map›Paper›PMID 28684784›Full record

ArticleScientific reports2017

Probing the missing mature β-cell proteomic landscape in differentiating patient iPSC-derived cells.

Heidrun Vethe, Yngvild Bjørlykke, Luiza M Ghila, Joao A Paulo, Hanne Scholz, Steven P Gygi, Simona Chera, Helge Ræder

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

41 citing papers in PubMed, 52 citations in OpenAlex.

  1. Review
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  5. Article
  6. Nanomedicine in the Treatment of Diabetes.International journal of molecular sciences · 2024
    Review
  7. Review
  8. Review
  9. Glucose Concentration in Regulating Induced Pluripotent Stem Cells Differentiation Toward Insulin-Producing Cells.Transplant international : official journal of the European Society for Organ Transplantation · 2024
    Article
  10. Review
  11. Article
  12. Review
  13. Review
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  15. Article
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  17. Article
  18. Article
  19. Maturity Onset Diabetes of the Young-New Approaches for Disease Modelling.International journal of molecular sciences · 2021
    Review
  20. Article
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

8 authors at 4 institutions in 2 countries.

Heidrun VetheKG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
Yngvild BjørlykkeDepartment of Pediatrics, Haukeland University Hospital, Bergen, Norway.
Luiza M GhilaKG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.ORCID 0000-0001-7173-6312
Joao A PauloDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4291-413X
Hanne ScholzDepartment of Transplant Medicine, Oslo University Hospital, Oslo, Norway.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Simona CheraKG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.ORCID 0000-0001-6310-3486
Helge RæderKG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway. Helge.Rader@uib.no.
University of Bergen · NOHarvard University · USHaukeland University Hospital · NOOslo University Hospital · NO

Funding

Resolving the role of nicotine-mediated phosphorylation on pancreatic fibrosisK01DK098285 · NIDDK · HARVARD MEDICAL SCHOOL · PI PAULO, JOAO A · 2013 to 2017
$638k
NIDDK NIH HHS K01 DK098285
6 · The paper itself

Abstract

MODY1 is a maturity-onset monogenic diabetes, caused by heterozygous mutations of the HNF4A gene. To date the cellular and molecular mechanisms leading to disease onset remain largely unknown. In this study, we demonstrate that insulin-positive cells can be generated in vitro from human induced pluripotent stem cells (hiPSCs) derived from patients carrying a non-sense HNF4A mutation, proving for the first time, that a human HNF4A mutation is neither blocking the expression of the insulin genes nor the development of insulin-producing cells in vitro. However, regardless of the mutation or diabetes status, these insulin-producing cells are immature, a common downfall off most current β-cell differentiation protocols. To further address the immature state of the cells, in vitro differentiated cells and adult human islets were compared by global proteomic analysis. We report the predicted upstream regulators and signalling pathways characterizing the proteome landscape of each entity. Subsequently, we focused on the molecular components absent or misregulated in the in vitro differentiated cells, to probe the components involved in the deficient in vitro maturation towards fully functional β-cells. This analysis identified the modulation of key developmental signalling pathways representing potential targets for improving the efficiency of the current differentiation protocols.

Indexed as

Cell DifferentiationAdultCell Culture TechniquesDiabetes Mellitus, Type 2FemaleHumansInduced Pluripotent Stem CellsInsulin-Secreting CellsIslets of LangerhansMaleModels, GeneticProteomeProteome

Identifiers

PMID28684784
PMCPMC5500592
OpenAlexW2724732749

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.