PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors derived from human pluripotent stem cells as a novel source of insulin‐secreting cells
<h3>Aim</h3><p dir="ltr">Beta cell replacement strategies are a promising alternative for diabetes treatment. Human pluripotent stem cells (hPSCs) serve as a scalable source for producing insulin-secreting cells for transplantation therapy. We recently generated novel hPS...
محفوظ في:
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| مؤلفون آخرون: | , , |
| منشور في: |
2020
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| الموضوعات: | |
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| _version_ | 1864513549617856512 |
|---|---|
| author | Bushra Memon (4792767) |
| author2 | Ihab Younis (57824) Fadhil Abubaker (14778163) Essam M. Abdelalim (5768072) |
| author2_role | author author author |
| author_facet | Bushra Memon (4792767) Ihab Younis (57824) Fadhil Abubaker (14778163) Essam M. Abdelalim (5768072) |
| author_role | author |
| dc.creator.none.fl_str_mv | Bushra Memon (4792767) Ihab Younis (57824) Fadhil Abubaker (14778163) Essam M. Abdelalim (5768072) |
| dc.date.none.fl_str_mv | 2020-08-28T21:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1002/dmrr.3400 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/PDX1__sup_sup__NKX6_1__sup_sup__progenitors_derived_from_human_pluripotent_stem_cells_as_a_novel_source_of_insulin_secreting_cells/22258000 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Endocrinology, Diabetes and Metabolism Beta cell replacement Human pluripotent stem cells (hPSCs) Pancreatic progenitors NKX6.1 PDX1 |
| dc.title.none.fl_str_mv | PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors derived from human pluripotent stem cells as a novel source of insulin‐secreting cells |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Aim</h3><p dir="ltr">Beta cell replacement strategies are a promising alternative for diabetes treatment. Human pluripotent stem cells (hPSCs) serve as a scalable source for producing insulin-secreting cells for transplantation therapy. We recently generated novel hPSC-derived pancreatic progenitors, expressing high levels of the transcription factor NKX6.1, in the absence of PDX1 (PDX1<sup>−</sup>/NKX6.1<sup>+</sup>). Herein, our aim was to characterize this novel population and assess its ability to differentiate into insulin-secreting beta cells in vitro.</p><h3>Materials and Methods</h3><p dir="ltr">Three different hPSC lines were differentiated into PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors, which were further differentiated into insulin-secreting cells using two different protocols. The progenitors and beta cells were extensively characterized. Transcriptome analysis was performed at different stages and compared with the profiles of various pancreatic counterparts.</p><h3>Results</h3><p dir="ltr">PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors expressed high levels of nestin, a key marker of pancreatic islet-derived progenitors, in the absence of E-cadherin, similar to pancreatic mesenchymal stem cells. At progenitor stage, comparison of the two populations showed downregulation of pancreatic epithelial genes and upregulation of neuronal development genes in PDX1<sup>−</sup>/NKX6.1<sup>+</sup> cells in comparison to the PDX1<sup>+</sup>/NKX6.1<sup>+</sup> cells. Interestingly, on further differentiation, PDX1<sup>−</sup>/NKX6.1<sup>+</sup> cells generated mono-hormonal insulin<sup>+</sup> cells and activated pancreatic key genes, such as PDX1. The transcriptome profile of PDX1<sup>−</sup>/NKX6.1<sup>+</sup>-derived beta (3D-beta) was closely similar to those of human pancreatic islets and purified hPSC-derived beta cells. Also, the 3D-beta cells secreted C-peptide in response to increased glucose concentrations indicating their functionality.</p><h3>Conclusion</h3><p dir="ltr">These findings provide a novel source of insulin-secreting cells that can be used for beta cell therapy for diabetes.</p><h2>Other Information</h2><p dir="ltr">Published in: Diabetes/Metabolism Research and Reviews<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1002/dmrr.3400" target="_blank">http://dx.doi.org/10.1002/dmrr.3400</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_d56ae2931a905f5a498a431b99c3b05a |
| identifier_str_mv | 10.1002/dmrr.3400 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/22258000 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors derived from human pluripotent stem cells as a novel source of insulin‐secreting cellsBushra Memon (4792767)Ihab Younis (57824)Fadhil Abubaker (14778163)Essam M. Abdelalim (5768072)Biomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsEndocrinology, Diabetes and MetabolismBeta cell replacementHuman pluripotent stem cells (hPSCs)Pancreatic progenitorsNKX6.1PDX1<h3>Aim</h3><p dir="ltr">Beta cell replacement strategies are a promising alternative for diabetes treatment. Human pluripotent stem cells (hPSCs) serve as a scalable source for producing insulin-secreting cells for transplantation therapy. We recently generated novel hPSC-derived pancreatic progenitors, expressing high levels of the transcription factor NKX6.1, in the absence of PDX1 (PDX1<sup>−</sup>/NKX6.1<sup>+</sup>). Herein, our aim was to characterize this novel population and assess its ability to differentiate into insulin-secreting beta cells in vitro.</p><h3>Materials and Methods</h3><p dir="ltr">Three different hPSC lines were differentiated into PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors, which were further differentiated into insulin-secreting cells using two different protocols. The progenitors and beta cells were extensively characterized. Transcriptome analysis was performed at different stages and compared with the profiles of various pancreatic counterparts.</p><h3>Results</h3><p dir="ltr">PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors expressed high levels of nestin, a key marker of pancreatic islet-derived progenitors, in the absence of E-cadherin, similar to pancreatic mesenchymal stem cells. At progenitor stage, comparison of the two populations showed downregulation of pancreatic epithelial genes and upregulation of neuronal development genes in PDX1<sup>−</sup>/NKX6.1<sup>+</sup> cells in comparison to the PDX1<sup>+</sup>/NKX6.1<sup>+</sup> cells. Interestingly, on further differentiation, PDX1<sup>−</sup>/NKX6.1<sup>+</sup> cells generated mono-hormonal insulin<sup>+</sup> cells and activated pancreatic key genes, such as PDX1. The transcriptome profile of PDX1<sup>−</sup>/NKX6.1<sup>+</sup>-derived beta (3D-beta) was closely similar to those of human pancreatic islets and purified hPSC-derived beta cells. Also, the 3D-beta cells secreted C-peptide in response to increased glucose concentrations indicating their functionality.</p><h3>Conclusion</h3><p dir="ltr">These findings provide a novel source of insulin-secreting cells that can be used for beta cell therapy for diabetes.</p><h2>Other Information</h2><p dir="ltr">Published in: Diabetes/Metabolism Research and Reviews<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1002/dmrr.3400" target="_blank">http://dx.doi.org/10.1002/dmrr.3400</a></p>2020-08-28T21:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1002/dmrr.3400https://figshare.com/articles/journal_contribution/PDX1__sup_sup__NKX6_1__sup_sup__progenitors_derived_from_human_pluripotent_stem_cells_as_a_novel_source_of_insulin_secreting_cells/22258000CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/222580002020-08-28T21:00:00Z |
| spellingShingle | PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors derived from human pluripotent stem cells as a novel source of insulin‐secreting cells Bushra Memon (4792767) Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Endocrinology, Diabetes and Metabolism Beta cell replacement Human pluripotent stem cells (hPSCs) Pancreatic progenitors NKX6.1 PDX1 |
| status_str | publishedVersion |
| title | PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors derived from human pluripotent stem cells as a novel source of insulin‐secreting cells |
| title_full | PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors derived from human pluripotent stem cells as a novel source of insulin‐secreting cells |
| title_fullStr | PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors derived from human pluripotent stem cells as a novel source of insulin‐secreting cells |
| title_full_unstemmed | PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors derived from human pluripotent stem cells as a novel source of insulin‐secreting cells |
| title_short | PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors derived from human pluripotent stem cells as a novel source of insulin‐secreting cells |
| title_sort | PDX1<sup>−</sup>/NKX6.1<sup>+</sup> progenitors derived from human pluripotent stem cells as a novel source of insulin‐secreting cells |
| topic | Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Endocrinology, Diabetes and Metabolism Beta cell replacement Human pluripotent stem cells (hPSCs) Pancreatic progenitors NKX6.1 PDX1 |