Evidence map›Paper›PMID 25901096›Full record

ArticleDiabetes2015

Dissecting Human Gene Functions Regulating Islet Development With Targeted Gene Transduction.

Philip T Pauerstein, Takuya Sugiyama, Susan E Stanley, Graeme W McLean, Jing Wang, Martín G Martín, Seung K Kim

Open access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Development (Cambridge, England) · 2018
    Article
  8. Article
  9. Article
  10. Article
  11. Research Resource: Genetic Labeling of Human Islet Alpha Cells.Molecular endocrinology (Baltimore, Md.) · 2016
    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

7 authors at 2 institutions in 1 country.

Philip T PauersteinDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA.
Takuya SugiyamaDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA.
Susan E StanleyDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA.
Graeme W McLeanDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA.
Jing WangDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA.
Martín G MartínDepartment of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
Seung K KimDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA seungkim@stanford.edu.
Stanford University · USUniversity of California, Los Angeles · US

Funding

Neurogenin3 and Intestinal FailureR01DK083762 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARTIN, MARTIN G · 2009 to 2012
$1.6M
Identifying Physiological and Molecular Inducers of Beta Cell MaturationF30DK102301 · NIDDK · STANFORD UNIVERSITY · PI PAUERSTEIN, PHILIP THOMAS · 2014 to 2016
$100k
Howard Hughes Medical InstituteNIDDK NIH HHS F30 DK102301NIDDK NIH HHS F30DK102301NIDDK NIH HHS R01 DK083762
6 · The paper itself

Abstract

During pancreas development, endocrine precursors and their progeny differentiate, migrate, and cluster to form nascent islets. The transcription factor Neurogenin 3 (Neurog3) is required for islet development in mice, but its role in these dynamic morphogenetic steps has been inferred from fixed tissues. Moreover, little is known about the molecular genetic functions of NEUROG3 in human islet development. We developed methods for gene transduction by viral microinjection in the epithelium of cultured Neurog3-null mutant fetal pancreas, permitting genetic complementation in a developmentally relevant context. In addition, we developed methods for quantitative assessment of live-cell phenotypes in single developing islet cells. Delivery of wild-type NEUROG3 rescued islet differentiation, morphogenesis, and live cell deformation, whereas the patient-derived NEUROG3(R107S) allele partially restored indicators of islet development. NEUROG3(P39X), a previously unreported patient allele, failed to restore islet differentiation or morphogenesis and was indistinguishable from negative controls, suggesting that it is a null mutation. Our systems also permitted genetic suppression analysis and revealed that targets of NEUROG3, including NEUROD1 and RFX6, can partially restore islet development in Neurog3-null mutant mouse pancreata. Thus, advances described here permitted unprecedented assessment of gene functions in regulating crucial dynamic aspects of islet development in the fetal pancreas.

Indexed as

Gene Expression Regulation, DevelopmentalAnimalsBasic Helix-Loop-Helix ProteinsCell DifferentiationCell LineageDNA-Binding ProteinsHumansIslets of LangerhansMiceMice, KnockoutNerve Tissue ProteinsRegulatory Factor X Transcription FactorsTranscription FactorsBasic Helix-Loop-Helix ProteinsDNA-Binding ProteinsNerve Tissue ProteinsNeurog3 protein, mouseNeurogenic differentiation factor 1Regulatory Factor X Transcription FactorsRfx6 protein, mouseTranscription Factors

Identifiers

PMID25901096
PMCPMC4512220
OpenAlexW2016750854

What OpenQuestion holds

Textmetadata
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.