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000277995 1001_ $$00000-0002-2817-1974$$aBreunig, Markus$$b0
000277995 245__ $$aPPDPF is not a key regulator of human pancreas development.
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000277995 520__ $$aGiven their capability to differentiate into each cell type of the human body, human pluripotent stem cells (hPSCs) provide a unique platform for developmental studies. In the current study, we employed this cell system to understand the role of pancreatic progenitor differentiation and proliferation factor (PPDPF), a protein that has been little explored so far. While the zebrafish orthologue exdpf is essential for exocrine pancreas specification, its importance for mammalian and human development has not been studied yet. We implemented a four times CRISPR/Cas9 nicking approach to knockout PPDPF in human embryonic stem cells (hESCs) and differentiated PPDPFKO/KO and PPDPFWT/WT cells towards the pancreatic lineage. In contrast to data obtained from zebrafish, a very modest effect of the knockout was observed in the development of pancreatic progenitors in vitro, not affecting lineage specification upon orthotopic transplantation in vivo. The modest effect is in line with the finding that genetic variants near PPDPF are associated with random glucose levels in humans, but not with type 2 diabetes risk, supporting that dysregulation of this gene may only result in minor alterations of glycaemic balance in humans. In addition, PPDPF is less organ- and cell type specifically expressed in higher vertebrates and its so far reported functions appear highly context-dependent.
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000277995 7001_ $$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
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