Zooming in on Diabetes Journal Club February 4, 2021
Zooming in on Diabetes Thursday, February 4 at 9:00 am (PST)
Presenter: Priye Iworima, Graduate Student – PhD program, Kieffer Lab, Life Sciences Institute, University of British Columbia (Vancouver)
Title: Aberrant development of pancreatic beta cells derived from human iPSCs with FOXA2 deficiency
Citation: Elsayed, A.K., Younis, I., Ali, G. et al. Aberrant development of pancreatic beta cells derived from human iPSCs with FOXA2 deficiency. Cell Death Dis 12, 103 (2021). https://doi.org/10.1038/s41419-021-03390-8
Abstract: FOXA2 has been identified as an essential factor for pancreas development and emerging evidence supports an association between FOXA2 and diabetes. Although the role of FOXA2 during pancreatic development is well-studied in animal models, its role during human islet cell development remains unclear. Here, we generated induced pluripotent stem cells (iPSCs) from a patient with FOXA2 haploinsufficiency (FOXA2+/− iPSCs) followed by beta-cell differentiation to understand the role of FOXA2 during pancreatic beta-cell development. Our results showed that FOXA2 haploinsufficiency resulted in aberrant expression of genes essential for the differentiation and proper functioning of beta cells. At pancreatic progenitor (PP2) and endocrine progenitor (EPs) stages, transcriptome analysis showed downregulation in genes associated with pancreatic development and diabetes and upregulation in genes associated with nervous system development and WNT signaling pathway. Knockout of FOXA2 in control iPSCs (FOXA2−/− iPSCs) led to severe phenotypes in EPs and beta-cell stages. The expression of NGN3 and its downstream targets at EPs as well as INSUILIN and GLUCAGON at the beta-cell stage, were almost absent in the cells derived from FOXA2−/− iPSCs. These findings indicate that FOXA2 is crucial for human pancreatic endocrine development and its defect may lead to diabetes based on FOXA2 dosage.
PMID: 33473118
“Zooming in on Diabetes” is a virtual journal club and was launched in March 2020.
It is a joint initiative across the University of British Columbia campuses including the Life Sciences Centre and the BC Children’s Hospital.
This Journal Club is designed for trainees to develop skills in critical evaluation of recent articles in the scientific literature related to diabetes research.
The intended audience are academic research trainees and faculty involved in diabetes research in British Columbia, Canada.
The journal club is held on Tuesdays and Thursdays via ZOOM.
