dc.contributor.author | Manea, T | |
dc.contributor.author | Nelson, JK | |
dc.contributor.author | Garrone, CM | |
dc.contributor.author | Hansson, K | |
dc.contributor.author | Evans, I | |
dc.contributor.author | Behrens, A | |
dc.contributor.author | Sancho, R | |
dc.date.accessioned | 2023-05-02T15:01:35Z | |
dc.date.available | 2023-05-02T15:01:35Z | |
dc.date.issued | 2023-04-28 | |
dc.identifier | 2457 | |
dc.identifier.citation | Nature Communications, 2023, 14 (1), | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5773 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-023-38146-9 | |
dc.description.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. | |
dc.language | en | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.relation.ispartof | Nature Communications | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.title | USP7 controls NGN3 stability and pancreatic endocrine lineage development. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-04-18 | |
dc.date.updated | 2023-05-02T14:54:20Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41467-023-38146-9 | |
rioxxterms.licenseref.startdate | 2023-04-28 | |
rioxxterms.type | Journal Article/Review | |
pubs.issue | 1 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Cancer Stem Cell | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1038/s41467-023-38146-9 | |
pubs.volume | 14 | |
icr.researchteam | Cancer Stem Cell | |
icr.researchteam | Convergence SC Management | |
dc.contributor.icrauthor | Evans, Ian | |
dc.contributor.icrauthor | Behrens, Axel | |
icr.provenance | Deposited by Dr Ian Evans on 2023-05-02. Deposit type is initial. No. of files: 1. Files: Manea et al 2023.pdf | |