000277995 001__ 277995 000277995 005__ 20250430100242.0 000277995 0247_ $$2doi$$a10.1371/journal.pgen.1011657 000277995 0247_ $$2pmid$$apmid:40193385 000277995 0247_ $$2ISSN$$a1553-7390 000277995 0247_ $$2ISSN$$a1553-7404 000277995 037__ $$aDZNE-2025-00522 000277995 041__ $$aEnglish 000277995 082__ $$a610 000277995 1001_ $$00000-0002-2817-1974$$aBreunig, Markus$$b0 000277995 245__ $$aPPDPF is not a key regulator of human pancreas development. 000277995 260__ $$aSan Francisco, Calif.$$bPublic Library of Science$$c2025 000277995 3367_ $$2DRIVER$$aarticle 000277995 3367_ $$2DataCite$$aOutput Types/Journal article 000277995 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1745919798_21727 000277995 3367_ $$2BibTeX$$aARTICLE 000277995 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000277995 3367_ $$00$$2EndNote$$aJournal Article 000277995 520__ $$aGiven their capability to differentiate into each cell type of the human body, human pluripotent stem cells (hPSCs) provide a unique platform for developmental studies. In the current study, we employed this cell system to understand the role of pancreatic progenitor differentiation and proliferation factor (PPDPF), a protein that has been little explored so far. While the zebrafish orthologue exdpf is essential for exocrine pancreas specification, its importance for mammalian and human development has not been studied yet. We implemented a four times CRISPR/Cas9 nicking approach to knockout PPDPF in human embryonic stem cells (hESCs) and differentiated PPDPFKO/KO and PPDPFWT/WT cells towards the pancreatic lineage. In contrast to data obtained from zebrafish, a very modest effect of the knockout was observed in the development of pancreatic progenitors in vitro, not affecting lineage specification upon orthotopic transplantation in vivo. The modest effect is in line with the finding that genetic variants near PPDPF are associated with random glucose levels in humans, but not with type 2 diabetes risk, supporting that dysregulation of this gene may only result in minor alterations of glycaemic balance in humans. In addition, PPDPF is less organ- and cell type specifically expressed in higher vertebrates and its so far reported functions appear highly context-dependent. 000277995 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0 000277995 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000277995 7001_ $$00000-0002-0640-0764$$aHohwieler, Meike$$b1 000277995 7001_ $$aHaderspeck, Jasmin$$b2 000277995 7001_ $$0P:(DE-2719)2811552$$aZweydorf, Felix$$b3 000277995 7001_ $$aHauff, Natalie$$b4 000277995 7001_ $$00009-0008-9051-3526$$aPasquini, Lino-Pascal$$b5 000277995 7001_ $$aWiegreffe, Christoph$$b6 000277995 7001_ $$00000-0002-2510-3140$$aZimmer, Eleni$$b7 000277995 7001_ $$aMulaw, Medhanie A$$b8 000277995 7001_ $$00000-0002-1538-0240$$aJulier, Cécile$$b9 000277995 7001_ $$aSimon, Eric$$b10 000277995 7001_ $$0P:(DE-2719)2811291$$aGloeckner, Christian Johannes$$b11$$udzne 000277995 7001_ $$00000-0003-0721-8187$$aLiebau, Stefan$$b12 000277995 7001_ $$00000-0003-0592-5232$$aKleger, Alexander$$b13 000277995 773__ $$0PERI:(DE-600)2186725-2$$a10.1371/journal.pgen.1011657$$gVol. 21, no. 4, p. e1011657 -$$n4$$pe1011657$$tPLoS Genetics$$v21$$x1553-7390$$y2025 000277995 8564_ $$uhttps://pub.dzne.de/record/277995/files/DZNE-2025-00522%20SUP.zip 000277995 8564_ $$uhttps://pub.dzne.de/record/277995/files/DZNE-2025-00522.pdf$$yOpenAccess 000277995 8564_ $$uhttps://pub.dzne.de/record/277995/files/DZNE-2025-00522.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000277995 909CO $$ooai:pub.dzne.de:277995$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery 000277995 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811552$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE 000277995 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811291$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b11$$kDZNE 000277995 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0 000277995 9141_ $$y2025 000277995 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bPLOS GENET : 2022$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2024-02-08T09:39:41Z 000277995 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2024-02-08T09:39:41Z 000277995 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2024-12-13 000277995 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000277995 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-13 000277995 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0 000277995 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-13 000277995 9201_ $$0I:(DE-2719)1210007$$kAG Gloeckner$$lFunctional Neuroproteomics and Translational Biomarkers in Neurodegenerative Diseases$$x0 000277995 980__ $$ajournal 000277995 980__ $$aVDB 000277995 980__ $$aUNRESTRICTED 000277995 980__ $$aI:(DE-2719)1210007 000277995 9801_ $$aFullTexts