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@ARTICLE{Breunig:277995,
author = {Breunig, Markus and Hohwieler, Meike and Haderspeck, Jasmin
and Zweydorf, Felix and Hauff, Natalie and Pasquini,
Lino-Pascal and Wiegreffe, Christoph and Zimmer, Eleni and
Mulaw, Medhanie A and Julier, Cécile and Simon, Eric and
Gloeckner, Christian Johannes and Liebau, Stefan and Kleger,
Alexander},
title = {{PPDPF} is not a key regulator of human pancreas
development.},
journal = {PLoS Genetics},
volume = {21},
number = {4},
issn = {1553-7390},
address = {San Francisco, Calif.},
publisher = {Public Library of Science},
reportid = {DZNE-2025-00522},
pages = {e1011657},
year = {2025},
abstract = {Given 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.},
cin = {AG Gloeckner},
ddc = {610},
cid = {I:(DE-2719)1210007},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40193385},
doi = {10.1371/journal.pgen.1011657},
url = {https://pub.dzne.de/record/277995},
}