p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic β-Cells
<p dir="ltr">The multipotent pancreatic progenitor cells (MPCs) co-expressing the transcription factors, PDX1 and NKX6.1, are the source of functional pancreatic β-cells. The aim of this study was to examine the effect of p53 inhibition in MPCs on the generation of PDX1+/NKX6.1+ MPCs...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | |
| منشور في: |
2023
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| الموضوعات: | |
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إضافة وسم
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| _version_ | 1864513530557890560 |
|---|---|
| author | Idil I. Aigha (14913774) |
| author2 | Essam M. Abdelalim (5768072) |
| author2_role | author |
| author_facet | Idil I. Aigha (14913774) Essam M. Abdelalim (5768072) |
| author_role | author |
| dc.creator.none.fl_str_mv | Idil I. Aigha (14913774) Essam M. Abdelalim (5768072) |
| dc.date.none.fl_str_mv | 2023-01-28T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s12015-023-10509-1 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/p53_Inhibition_in_Pancreatic_Progenitors_Enhances_the_Differentiation_of_Human_Pluripotent_Stem_Cells_into_Pancreatic_-Cells/24998288 |
| 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 Biomedical and clinical sciences Medical biochemistry and metabolomics Medical biotechnology hESCs Diferentiation protocol NKX6.1 Insulin Islets Monohormonal β-cells |
| dc.title.none.fl_str_mv | p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic β-Cells |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">The multipotent pancreatic progenitor cells (MPCs) co-expressing the transcription factors, PDX1 and NKX6.1, are the source of functional pancreatic β-cells. The aim of this study was to examine the effect of p53 inhibition in MPCs on the generation of PDX1+/NKX6.1+ MPCs and pancreatic β-cell generation. Human embryonic stem cells (hESCs) were differentiated into MPCs and β-cells. hESC-MPCs (stage 4) were treated with different concentrations of p53 inhibitors, and their effect was evaluated using different approaches. NKX6.1 was overexpressed during MPCs specification. Inhibition of p53 using pifithrin-μ (PFT-μ) at the MPC stage resulted in a significant increase in the number of PDX1+/NKX6.1+ cells and a reduction in the number of CHGA+/NKX6.1− cells. Further differentiation of MPCs treated with PFT-μ into pancreatic β-cells showed that PFT-μ treatment did not significantly change the number of C-Peptide+ cells; however, the number of C-PEP+ cells co-expressing glucagon (polyhormonal) was significantly reduced in the PFT-μ treated cells. Interestingly, overexpression of NKX6.1 in hESC-MPCs enhanced the expression of key MPC genes and dramatically suppressed p53 expression. Our findings demonstrated that the p53 inhibition during stage 4 of differentiation enhanced MPC generation, prevented premature endocrine induction and favored the differentiation into monohormonal β-cells. These findings suggest that adding a p53 inhibitor to the differentiation media can significantly enhance the generation of monohormonal β-cells.</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/s12015-023-10509-1" target="_blank">https://dx.doi.org/10.1007/s12015-023-10509-1</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_e02578a89eef283bee8c3e1443c5e1e7 |
| identifier_str_mv | 10.1007/s12015-023-10509-1 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/24998288 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic β-CellsIdil I. Aigha (14913774)Essam M. Abdelalim (5768072)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesMedical biochemistry and metabolomicsMedical biotechnologyhESCsDiferentiation protocolNKX6.1InsulinIsletsMonohormonal β-cells<p dir="ltr">The multipotent pancreatic progenitor cells (MPCs) co-expressing the transcription factors, PDX1 and NKX6.1, are the source of functional pancreatic β-cells. The aim of this study was to examine the effect of p53 inhibition in MPCs on the generation of PDX1+/NKX6.1+ MPCs and pancreatic β-cell generation. Human embryonic stem cells (hESCs) were differentiated into MPCs and β-cells. hESC-MPCs (stage 4) were treated with different concentrations of p53 inhibitors, and their effect was evaluated using different approaches. NKX6.1 was overexpressed during MPCs specification. Inhibition of p53 using pifithrin-μ (PFT-μ) at the MPC stage resulted in a significant increase in the number of PDX1+/NKX6.1+ cells and a reduction in the number of CHGA+/NKX6.1− cells. Further differentiation of MPCs treated with PFT-μ into pancreatic β-cells showed that PFT-μ treatment did not significantly change the number of C-Peptide+ cells; however, the number of C-PEP+ cells co-expressing glucagon (polyhormonal) was significantly reduced in the PFT-μ treated cells. Interestingly, overexpression of NKX6.1 in hESC-MPCs enhanced the expression of key MPC genes and dramatically suppressed p53 expression. Our findings demonstrated that the p53 inhibition during stage 4 of differentiation enhanced MPC generation, prevented premature endocrine induction and favored the differentiation into monohormonal β-cells. These findings suggest that adding a p53 inhibitor to the differentiation media can significantly enhance the generation of monohormonal β-cells.</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/s12015-023-10509-1" target="_blank">https://dx.doi.org/10.1007/s12015-023-10509-1</a></p>2023-01-28T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s12015-023-10509-1https://figshare.com/articles/journal_contribution/p53_Inhibition_in_Pancreatic_Progenitors_Enhances_the_Differentiation_of_Human_Pluripotent_Stem_Cells_into_Pancreatic_-Cells/24998288CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/249982882023-01-28T03:00:00Z |
| spellingShingle | p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic β-Cells Idil I. Aigha (14913774) Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical biochemistry and metabolomics Medical biotechnology hESCs Diferentiation protocol NKX6.1 Insulin Islets Monohormonal β-cells |
| status_str | publishedVersion |
| title | p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic β-Cells |
| title_full | p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic β-Cells |
| title_fullStr | p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic β-Cells |
| title_full_unstemmed | p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic β-Cells |
| title_short | p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic β-Cells |
| title_sort | p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic β-Cells |
| topic | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical biochemistry and metabolomics Medical biotechnology hESCs Diferentiation protocol NKX6.1 Insulin Islets Monohormonal β-cells |