Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model
<p dir="ltr">The pathogenesis of diabetes involves complex changes in the expression profiles of mRNA and non-coding RNAs within pancreatic islet cells. Recent progress in induced pluripotent stem cell (iPSC) technology have allowed the modeling of diabetes-associated genes. Our rece...
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| مؤلفون آخرون: | , , |
| منشور في: |
2024
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| _version_ | 1864513510279479296 |
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| author | Ahmed K. Elsayed (13275302) |
| author2 | Noura Aldous (15429873) Nehad M. Alajez (7397276) Essam M. Abdelalim (5768072) |
| author2_role | author author author |
| author_facet | Ahmed K. Elsayed (13275302) Noura Aldous (15429873) Nehad M. Alajez (7397276) Essam M. Abdelalim (5768072) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ahmed K. Elsayed (13275302) Noura Aldous (15429873) Nehad M. Alajez (7397276) Essam M. Abdelalim (5768072) |
| dc.date.none.fl_str_mv | 2024-06-25T12:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s12015-024-10752-0 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Identifying_miRNA_Signatures_Associated_with_Pancreatic_Islet_Dysfunction_in_a_FOXA2-Deficient_iPSC_Model/26363152 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Pancreatic development Transcription factors β-cells miRNA profile |
| dc.title.none.fl_str_mv | Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">The pathogenesis of diabetes involves complex changes in the expression profiles of mRNA and non-coding RNAs within pancreatic islet cells. Recent progress in induced pluripotent stem cell (iPSC) technology have allowed the modeling of diabetes-associated genes. Our recent study using FOXA2-deficient human iPSC models has highlighted an essential role for FOXA2 in the development of human pancreas. Here, we aimed to provide further insights on the role of microRNAs (miRNAs) by studying the miRNA-mRNA regulatory networks in iPSC-derived islets lacking the FOXA2 gene. Consistent with our previous findings, the absence of FOXA2 significantly downregulated the expression of islet hormones, INS, and GCG, alongside other key developmental genes in pancreatic islets. Concordantly, RNA-Seq analysis showed significant downregulation of genes related to pancreatic development and upregulation of genes associated with nervous system development and lipid metabolic pathways. Furthermore, the absence of FOXA2 in iPSC-derived pancreatic islets resulted in significant alterations in miRNA expression, with 61 miRNAs upregulated and 99 downregulated. The upregulated miRNAs targeted crucial genes involved in diabetes and pancreatic islet cell development. In contrary, the absence of FOXA2 in islets showed a network of downregulated miRNAs targeting genes related to nervous system development and lipid metabolism. These findings highlight the impact of FOXA2 absence on pancreatic islet development and suggesting intricate miRNA-mRNA regulatory networks affecting pancreatic islet cell development.</p><h2>Other Information</h2><p dir="ltr">Published in: Stem Cell Reviews and Reports<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/10.1007/s12015-024-10752-0" target="_blank">https://dx.doi.org/10.1007/s12015-024-10752-0</a></p><p dir="ltr">Additional institutions affiliated with: Translational Cancer and Immunity Center - QBRI</p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_3cd4665adbbd613a279ad8887600b93d |
| identifier_str_mv | 10.1007/s12015-024-10752-0 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26363152 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC ModelAhmed K. Elsayed (13275302)Noura Aldous (15429873)Nehad M. Alajez (7397276)Essam M. Abdelalim (5768072)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsPancreatic developmentTranscription factorsβ-cellsmiRNA profile<p dir="ltr">The pathogenesis of diabetes involves complex changes in the expression profiles of mRNA and non-coding RNAs within pancreatic islet cells. Recent progress in induced pluripotent stem cell (iPSC) technology have allowed the modeling of diabetes-associated genes. Our recent study using FOXA2-deficient human iPSC models has highlighted an essential role for FOXA2 in the development of human pancreas. Here, we aimed to provide further insights on the role of microRNAs (miRNAs) by studying the miRNA-mRNA regulatory networks in iPSC-derived islets lacking the FOXA2 gene. Consistent with our previous findings, the absence of FOXA2 significantly downregulated the expression of islet hormones, INS, and GCG, alongside other key developmental genes in pancreatic islets. Concordantly, RNA-Seq analysis showed significant downregulation of genes related to pancreatic development and upregulation of genes associated with nervous system development and lipid metabolic pathways. Furthermore, the absence of FOXA2 in iPSC-derived pancreatic islets resulted in significant alterations in miRNA expression, with 61 miRNAs upregulated and 99 downregulated. The upregulated miRNAs targeted crucial genes involved in diabetes and pancreatic islet cell development. In contrary, the absence of FOXA2 in islets showed a network of downregulated miRNAs targeting genes related to nervous system development and lipid metabolism. These findings highlight the impact of FOXA2 absence on pancreatic islet development and suggesting intricate miRNA-mRNA regulatory networks affecting pancreatic islet cell development.</p><h2>Other Information</h2><p dir="ltr">Published in: Stem Cell Reviews and Reports<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/10.1007/s12015-024-10752-0" target="_blank">https://dx.doi.org/10.1007/s12015-024-10752-0</a></p><p dir="ltr">Additional institutions affiliated with: Translational Cancer and Immunity Center - QBRI</p>2024-06-25T12:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s12015-024-10752-0https://figshare.com/articles/journal_contribution/Identifying_miRNA_Signatures_Associated_with_Pancreatic_Islet_Dysfunction_in_a_FOXA2-Deficient_iPSC_Model/26363152CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/263631522024-06-25T12:00:00Z |
| spellingShingle | Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model Ahmed K. Elsayed (13275302) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Pancreatic development Transcription factors β-cells miRNA profile |
| status_str | publishedVersion |
| title | Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model |
| title_full | Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model |
| title_fullStr | Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model |
| title_full_unstemmed | Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model |
| title_short | Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model |
| title_sort | Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Pancreatic development Transcription factors β-cells miRNA profile |