Genome-wide differential expression profiling of long non-coding RNAs (lncRNAs) in pancreatic cells derived from FOXA2-/- iPSCs

Poster by Ahmed K. Elsayed, Nehad M. Alajez, and Essam M. Abdelalim (Hamad Bin Khalifa University)

Background: Our recent studies showed that FOXA2 plays a key role in the development of endocrine and exocrine pancreas. Downregulation of FOXA2 expression during differentiation of induced pluripotent stem cells (iPSCs) into pancreatic islets leads to a significant reduction in α-and β-cell masses. However, whether these changes are associated with alterations in the expression profile of the long non-coding RNAs (lncRNAs) remains unclear.

Objective: the objective of this study is to investigate the alterations in the lncRNA profile and its relationship with the dysregulated mRNAs at the pancreatic progenitors (PPs) and pancreatic islet stages lacking FOXA2.

Methods: Therefore, here, we used our recently established iPSCs lacking FOXA2 (FOXA2-/- iPSCs). we screened the dysregulated lncRNAs in the pancreatic progenitors (PPs) and β-cell stage derived from FOXA2-/- iPSCs in comparison to its control.

Results: PPs and islet cells lacking FOXA2 showed several dysregulated lncRNAs in comparison to controls. Differential expression analysis identified 442 downregulated and 114 upregulated lncRNAs in PPs and 177 downregulated and 59 upregulated in the β-cell stage. Correlation analysis revealed 12 DE-lncRNAs, which were strongly correlated to key downregulated pancreatic genes in both pancreatic progenitors and beta cell stages (MEG3, H19, ZNF667-AS1, LINC00543, LINC00261, AC097639.1, AL035661.1, SLC25A25-AS1, U73166.1, ZNF790-AS1, MNX1-AS2, and AC091563.1).

Conclusion: Our results showed a strong correlation of lncRNAs to several key pancreatic genes and TFs during pancreatic differentiation. Furthermore, these data suggest that the FOXA2-related defective pancreatic islet development is associated with significant alterations in the expression profile of lncRNAs.