Evidence map›Paper›PMID 24374552›Full record

ArticleDiabetologia2014

Aldehyde dehydrogenase 1 activity in the developing human pancreas modulates retinoic acid signalling in mediating islet differentiation and survival.

Jinming Li, Zhi C Feng, Frances S-H Yeung, Melanie R-M Wong, Amanda Oakie, George F Fellows, Cynthia G Goodyer, David A Hess, Rennian Wang

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In one paragraph

Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
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  17. Evidence of β-Cell Dedifferentiation in Human Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2016
    Article
  18. Retinoids in the pancreas.Hepatobiliary surgery and nutrition · 2016
    Review
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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

9 authors at 3 institutions in 1 country.

Jinming LiChildren's Health Research Institute, Western University, 800 Commissioners Road East, London, ON, Canada, N6C 2V5.
Zhi C Feng
Frances S-H Yeung
Melanie R-M Wong
Amanda Oakie
George F Fellows
Cynthia G Goodyer
David A Hess
Rennian Wang
Children’s Health Research Institute · CAWestern University · CAMcGill University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisAldehyde dehydrogenase 1 (ALDH1), a human stem-cell marker, is an enzyme responsible for converting retinaldehydes to retinoic acids (RAs) to modulate cell differentiation. However, data on expression levels and functional roles of ALDH1 during human fetal pancreatic development are limited. The focus of this study was to characterise ALDH1 expression patterns and to determine its functional role in islet cell differentiation.

methodsThe presence of ALDH1 in the human fetal pancreas (8-22 weeks) was characterised by microarray, quantitative RT-PCR, western blotting and immunohistological approaches. Isolated human fetal islet-epithelial cell clusters were treated with ALDH1 inhibitors, retinoic acid receptor (RAR) agonists and ALDH1A1 small interfering (si)RNA.

resultsIn the developing human pancreatic cells, high ALDH1 activity frequently co-localised with key stem-cell markers as well as endocrine transcription factors. A high level of ALDH1 was expressed in newly differentiated insulin(+) cells and this decreased as development progressed. Pharmacological inhibition of ALDH1 activity in human fetal islet-epithelial cell clusters resulted in reduced endocrine cell differentiation and increased cell apoptosis, and was reversed with co-treatment of RAR/RXR agonists. Furthermore, siRNA knockdown of ALDH1A1 significantly decreased RAR expression and induced cell apoptosis via suppression of the phosphoinositide 3-kinase (PI3K) pathway and activation of caspase signals. CONCLUSIONS/

interpretationOur findings indicate that ALDH1(+) cells represent a pool of endocrine precursors in the developing human pancreas and that ALDH1 activity is required during endocrine cell differentiation. Inhibition of ALDH1-mediated retinoid signalling impairs human fetal islet cell differentiation and survival.

Indexed as

Aldehyde Dehydrogenase 1 FamilyBlotting, WesternFemaleFluorescent Antibody TechniqueGene Expression Regulation, DevelopmentalHumansIslets of LangerhansIsoenzymesPancreasPregnancyRetinal DehydrogenaseTretinoinAldehyde Dehydrogenase 1 FamilyALDH1A1 protein, humanIsoenzymesRetinal DehydrogenaseTretinoin

Identifiers

PMID24374552
OpenAlexW2058829024

What OpenQuestion holds

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Read underepoch 390

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.