RNASeq of PAX4 KO vs WT in 7 stages of differentiation from human iPSCs to BLC

Transcriptomes were profiled along with the differentiation from human induced pluripotent stem cell (iPSC) to beta-like cell (BLC) with PAX4 knocked out or not.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 2 Publications

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Dataset ID	Description	Technology	Samples
EGAD50000000516	The coding variant (p.Arg192His) in the transcription factor PAX4 is associated with an altered risk for type 2 diabetes (T2D) in East Asian populations. In mice, Pax4 is essential for beta cell formation but its role on human beta cell development and/or function is unknown. Participants carrying the PAX4 p.His192 allele exhibited decreased pancreatic beta cell function compared to homozygotes for the p.192Arg allele in a cross-sectional study in which we carried out an intravenous glucose tolerance test and an oral glucose tolerance test. In a pedigree of a patient with young onset diabetes, several members carry a newly identified p.Tyr186X allele. In the human beta cell model, EndoC-βH1, PAX4 knockdown led to impaired insulin secretion, reduced total insulin content, and altered hormone gene expression. Deletion of PAX4 in human induced pluripotent stem cell (hiPSC)-derived islet-like cells resulted in derepression of alpha cell gene expression. In vitro differentiation of hiPSCs carrying PAX4 p.His192 and p.X186 risk alleles exhibited increased polyhormonal endocrine cell formation and reduced insulin content that can be reversed with gene correction. Together, we demonstrate the role of PAX4 in human endocrine cell development, beta cell function, and its contribution to T2D-risk.	Illumina NovaSeq 6000	64

Publications	Citations
PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development. Lau HH, Krentz NAJ, Abaitua F, Perez-Alcantara M, Chan JW, Ajeian J, Ghosh S, Lee Y, Yang J, Thaman S, Champon B, Sun H, Jha A, Hoon S, Tan NS, Gardner DS, Kao SL, Tai ES, Gloyn AL, Teo AKK. Nat Commun 14: 2023 6119	23
Complete loss of PAX4 causes transient neonatal diabetes in humans. Russ-Silsby J, Lee Y, Rajesh V, Amoli M, Mirhosseini NA, Godbole T, Johnson MB, Ibarra DE, Sun H, Krentz NAJ, Wakeling MN, Flanagan SE, Hattersley AT, Gloyn AL, De Franco E. Mol Metab 99: 2025 102201	0