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Updated: Jul 17, 2025
Efficient Generation and Editing of Feeder-free IPSCs from Human Pancreatic Cells Using the CRISPR-Cas9 System
Published on: November 8, 2017
Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells
Ahmed K Elsayed1,2,3, Nehad M Alajez3,4, Essam M Abdelalim5,6
1Diabetes Research Center (DRC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), PO Box 34110, Doha, Qatar.
Background:
Our recent studies have demonstrated the crucial involvement of FOXA2 in the development of human pancreas. Reduction of FOXA2 expression during the differentiation of induced pluripotent stem cells (iPSCs) into pancreatic islets has been found to reduce α-and β-cell masses. However, the extent to which such changes are linked to alterations in the expression profile of long non-coding RNAs (lncRNAs) remains unraveled.
Methods:
Here, we employed our recently established FOXA2-deficient iPSCs (FOXA2-/- iPSCs) to investigate changes in lncRNA profiles and their correlation with dysregulated mRNAs during the pancreatic progenitor (PP) and pancreatic islet stages. Furthermore, we constructed co-expression networks linking significantly downregulated lncRNAs with differentially expressed pancreatic mRNAs.
Results:
Our results showed that 442 lncRNAs were downregulated, and 114 lncRNAs were upregulated in PPs lacking FOXA2 compared to controls. Similarly, 177 lncRNAs were downregulated, and 59 lncRNAs were upregulated in islet cells lacking FOXA2 compared to controls. At both stages, we observed a strong correlation between lncRNAs and several crucial pancreatic genes and TFs during pancreatic differentiation. Correlation analysis revealed 12 DE-lncRNAs that strongly correlated with key downregulated pancreatic genes in both PPs and islet cell stages. Selected DE-lncRNAs were validated using RT-qPCR.
Conclusions:
Our data indicate that the observed defects in pancreatic islet development due to the FOXA2 loss is associated with significant alterations in the expression profile of lncRNAs. Therefore, our findings provide novel insights into the role of lncRNA and mRNA networks in regulating pancreatic islet development, which warrants further investigations. Video Abstract.
Insights
Loss of FOXA2 impacts human pancreas development by altering long non-coding RNA (lncRNA) profiles. This study reveals lncRNA-mRNA networks crucial for pancreatic islet formation, offering new therapeutic targets.
Area of Science:
- Stem cell biology
- Developmental biology
- Genomics
Background:
- Forkhead box A2 (FOXA2) is vital for human pancreas development.
- Reduced FOXA2 in induced pluripotent stem cells (iPSCs) impairs pancreatic islet cell mass.
- The role of long non-coding RNAs (lncRNAs) in FOXA2-mediated pancreatic development is unclear.
Discussion:
- FOXA2 deficiency in iPSCs alters lncRNA expression during pancreatic progenitor and islet differentiation.
- Co-expression networks reveal links between downregulated lncRNAs and dysregulated pancreatic mRNAs.
- Specific lncRNA-mRNA interactions are conserved across pancreatic differentiation stages.
Key Insights:
- Significant changes in lncRNA profiles (downregulation and upregulation) occur in FOXA2-deficient pancreatic progenitors and islet cells.
- A strong correlation exists between lncRNAs and key pancreatic genes/transcription factors.
- Twelve differentially expressed lncRNAs (DE-lncRNAs) strongly correlate with downregulated pancreatic genes in both stages.
Outlook:
- FOXA2-dependent pancreatic islet development defects are linked to lncRNA expression alterations.
- lncRNA-mRNA networks play a critical role in regulating pancreatic islet development.
- Further research into these networks may uncover novel therapeutic strategies for pancreatic diseases.
