Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells
<h3>Background</h3><p dir="ltr">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 f...
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2023
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| _version_ | 1864513526862708736 |
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| author | Ahmed K. Elsayed (13275302) |
| author2 | Nehad M. Alajez (7397276) Essam M. Abdelalim (5768072) |
| author2_role | author author |
| author_facet | Ahmed K. Elsayed (13275302) Nehad M. Alajez (7397276) Essam M. Abdelalim (5768072) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ahmed K. Elsayed (13275302) Nehad M. Alajez (7397276) Essam M. Abdelalim (5768072) |
| dc.date.none.fl_str_mv | 2023-09-05T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s12964-023-01212-2 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Genome-wide_differential_expression_profiling_of_long_non-coding_RNAs_in_FOXA2_knockout_iPSC-derived_pancreatic_cells/25256689 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology β-cell development lncRNAs Epigenetic mRNA profle Pancreatic islets |
| dc.title.none.fl_str_mv | Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Background</h3><p dir="ltr">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.</p><h3>Methods</h3><p dir="ltr">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.</p><h3>Results</h3><p dir="ltr">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.</p><h3>Conclusions</h3><p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Cell Communication and Signaling<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12964-023-01212-2" target="_blank">https://dx.doi.org/10.1186/s12964-023-01212-2</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_b5dc167695a24d6e60ec388d953b8a46 |
| identifier_str_mv | 10.1186/s12964-023-01212-2 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25256689 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cellsAhmed K. Elsayed (13275302)Nehad M. Alajez (7397276)Essam M. Abdelalim (5768072)Biological sciencesBiochemistry and cell biologyβ-cell developmentlncRNAsEpigeneticmRNA proflePancreatic islets<h3>Background</h3><p dir="ltr">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.</p><h3>Methods</h3><p dir="ltr">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.</p><h3>Results</h3><p dir="ltr">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.</p><h3>Conclusions</h3><p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Cell Communication and Signaling<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12964-023-01212-2" target="_blank">https://dx.doi.org/10.1186/s12964-023-01212-2</a></p>2023-09-05T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s12964-023-01212-2https://figshare.com/articles/journal_contribution/Genome-wide_differential_expression_profiling_of_long_non-coding_RNAs_in_FOXA2_knockout_iPSC-derived_pancreatic_cells/25256689CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/252566892023-09-05T03:00:00Z |
| spellingShingle | Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells Ahmed K. Elsayed (13275302) Biological sciences Biochemistry and cell biology β-cell development lncRNAs Epigenetic mRNA profle Pancreatic islets |
| status_str | publishedVersion |
| title | Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells |
| title_full | Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells |
| title_fullStr | Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells |
| title_full_unstemmed | Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells |
| title_short | Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells |
| title_sort | Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells |
| topic | Biological sciences Biochemistry and cell biology β-cell development lncRNAs Epigenetic mRNA profle Pancreatic islets |