Evidence map›Paper›PMID 37117185›Full record

ArticleNature communications2023

USP7 controls NGN3 stability and pancreatic endocrine lineage development.

Teodora Manea, Jessica Kristine Nelson, Cristina Maria Garrone, Karin Hansson, Ian Evans, Axel Behrens, Rocio Sancho

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. 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
4.4field-weighted citation impact, top 5% 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

12 citing papers in PubMed, 14 citations in OpenAlex.

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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

7 authors at 2 institutions in 2 countries.

Teodora Manea *Centre for Gene Therapy and Regenerative Medicine, King's College London, London, UK.ORCID 0000-0002-4404-086X
Jessica Kristine Nelson *Adult Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Cristina Maria GarroneCentre for Gene Therapy and Regenerative Medicine, King's College London, London, UK.ORCID 0000-0002-8085-7981
Karin HanssonCancer Stem Cell Laboratory, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK.ORCID 0000-0002-6993-7673
Ian EvansAdult Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.ORCID 0000-0002-0468-8274
Axel BehrensAdult Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.ORCID 0000-0002-1557-1143
Rocio SanchoCentre for Gene Therapy and Regenerative Medicine, King's College London, London, UK. rocio.sancho@kcl.ac.uk.ORCID 0000-0002-4894-5391
Institute of Cancer Research · GBKing's College London · GB

Funding

Cancer Research UK FC001039Medical Research Council FC001039Medical Research Council MR/S000011/1Medical Research Council MR/T015470/1Wellcome Trust 215138/Z/18/ZWellcome Trust 218461/Z/19/ZWellcome Trust FC001039
6 · The paper itself

Abstract

Understanding the factors and mechanisms involved in beta-cell development will guide therapeutic efforts to generate fully functional beta cells for diabetes. Neurogenin 3 (NGN3) is the key transcription factor that marks endocrine progenitors and drives beta-cell differentiation. Here we screen for binding partners of NGN3 and identify the deubiquitylating enzyme USP7 as a key regulator of NGN3 stability. Mechanistically, USP7 interacts with, deubiquitinates and stabilizes NGN3. In vivo, conditional knockout of Usp7 in the mouse embryonic pancreas causes a dramatic reduction in islet formation and hyperglycemia in adult mice, due to impaired NGN3-mediated endocrine specification during pancreatic development. Furthermore, pharmacological inhibition of USP7 during endocrine specification in human iPSC models of beta-cell differentiation decreases NGN3 expressing progenitor cell numbers and impairs beta cell differentiation. Thus, the USP7-NGN3 axis is an essential mechanism for driving endocrine development and beta-cell differentiation, which can be therapeutically exploited.

Indexed as

Islets of LangerhansAdultAnimalsBasic Helix-Loop-Helix ProteinsCell DifferentiationHumansMiceNerve Tissue ProteinsPancreasTranscription FactorsUbiquitin-Specific Peptidase 7Basic Helix-Loop-Helix ProteinsNerve Tissue ProteinsNEUROG3 protein, humanNeurog3 protein, mouseTranscription FactorsUbiquitin-Specific Peptidase 7USP7 protein, human

Identifiers

PMID37117185
PMCPMC10147604
OpenAlexW4367297520

What OpenQuestion holds

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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.