Differentiation of human pluripotent stem cells into two distinct NKX6.1 populations of pancreatic progenitors
<h3>Background</h3><p dir="ltr">The expression of a specific combination of transcription factors (TFs) in the multipotent progenitor cells (MPCs) is critical for determining pancreatic cell fate. NKX6.1 expression in PDX1<sup>+</sup> MPCs is required for func...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | , , |
| Published: |
2018
|
| Subjects: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1864513513365438464 |
|---|---|
| author | Idil I. Aigha (14913774) |
| author2 | Bushra Memon (4792767) Ahmed K. Elsayed (13275302) Essam M. Abdelalim (5768072) |
| author2_role | author author author |
| author_facet | Idil I. Aigha (14913774) Bushra Memon (4792767) Ahmed K. Elsayed (13275302) Essam M. Abdelalim (5768072) |
| author_role | author |
| dc.creator.none.fl_str_mv | Idil I. Aigha (14913774) Bushra Memon (4792767) Ahmed K. Elsayed (13275302) Essam M. Abdelalim (5768072) |
| dc.date.none.fl_str_mv | 2018-04-03T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s13287-018-0834-0 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Differentiation_of_human_pluripotent_stem_cells_into_two_distinct_NKX6_1_populations_of_pancreatic_progenitors/25921105 |
| 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 Medical biotechnology hESCs hiPSCs Pancreatic development Transcription factors Pancreatic progenitors β cells |
| dc.title.none.fl_str_mv | Differentiation of human pluripotent stem cells into two distinct NKX6.1 populations of pancreatic progenitors |
| 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">The expression of a specific combination of transcription factors (TFs) in the multipotent progenitor cells (MPCs) is critical for determining pancreatic cell fate. NKX6.1 expression in PDX1<sup>+</sup> MPCs is required for functional β cell generation. We have recently demonstrated the generation of a novel population of human pluripotent stem cell (hPSC)-derived MPCs that exclusively express NKX6.1, independently of PDX1 (PDX1<sup>−</sup>/NKX6.1<sup>+</sup>). Therefore, the aim of this study was to characterize this novel population to elucidate its role in pancreatic development.</p><h3>Methods</h3><p dir="ltr">The hPSCs were exposed to two differentiation protocols to generate MPCs that were analyzed using different techniques.</p><h3>Results</h3><p dir="ltr">Based on the expression of PDX1 and NKX6.1, we generated three different populations of MPCs, two of them were NKX6.1<sup>+</sup>. One of these NKX6.1 populations coexpressed PDX1 (PDX1<sup>+</sup>/NKX6.1<sup>+</sup>) which is known to mature into functional β cells, and an additional novel population did not express PDX1 (PDX1<sup>−</sup>/NKX6.1<sup>+</sup>) with an undefined role in pancreatic cell fate. This novel population was enriched using our recently established protocol, allowing their reorganization in three-dimensional (3D) structures. Since NKX6.1 induction in MPCs can direct them to endocrine and/or ductal cells in humans, we examined the coexpression of endocrine and ductal markers. We found that the expression of the pancreatic endocrine progenitor markers chromogranin A (CHGA) and neurogenin 3 (NGN3) was not detected in the NKX6.1<sup>+</sup> 3D structures, while few structures were positive for NKX2.2, another endocrine progenitor marker, thereby shedding light on the origin of this novel population and its role in pancreatic endocrine development. Furthermore, SOX9 was highly expressed in the 3D structures, but cytokeratin 19, a main ductal marker, was not detected in these structures.</p><h3>Conclusions</h3><p dir="ltr">These data support the existence of two independent NKX6.1<sup>+</sup> MPC populations during human pancreatic development and the novel PDX1<sup>−</sup>/NKX6.1<sup>+</sup> population may be involved in a unique trajectory to generate β cells in humans.</p><h2>Other Information</h2><p dir="ltr">Published in: Stem Cell Research & Therapy<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="https://dx.doi.org/10.1186/s13287-018-0834-0" target="_blank">https://dx.doi.org/10.1186/s13287-018-0834-0</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_9f8c02010758a9c12e2677e842ac7419 |
| identifier_str_mv | 10.1186/s13287-018-0834-0 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25921105 |
| publishDate | 2018 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Differentiation of human pluripotent stem cells into two distinct NKX6.1 populations of pancreatic progenitorsIdil I. Aigha (14913774)Bushra Memon (4792767)Ahmed K. Elsayed (13275302)Essam M. Abdelalim (5768072)Biomedical and clinical sciencesMedical biotechnologyhESCshiPSCsPancreatic developmentTranscription factorsPancreatic progenitorsβ cells<h3>Background</h3><p dir="ltr">The expression of a specific combination of transcription factors (TFs) in the multipotent progenitor cells (MPCs) is critical for determining pancreatic cell fate. NKX6.1 expression in PDX1<sup>+</sup> MPCs is required for functional β cell generation. We have recently demonstrated the generation of a novel population of human pluripotent stem cell (hPSC)-derived MPCs that exclusively express NKX6.1, independently of PDX1 (PDX1<sup>−</sup>/NKX6.1<sup>+</sup>). Therefore, the aim of this study was to characterize this novel population to elucidate its role in pancreatic development.</p><h3>Methods</h3><p dir="ltr">The hPSCs were exposed to two differentiation protocols to generate MPCs that were analyzed using different techniques.</p><h3>Results</h3><p dir="ltr">Based on the expression of PDX1 and NKX6.1, we generated three different populations of MPCs, two of them were NKX6.1<sup>+</sup>. One of these NKX6.1 populations coexpressed PDX1 (PDX1<sup>+</sup>/NKX6.1<sup>+</sup>) which is known to mature into functional β cells, and an additional novel population did not express PDX1 (PDX1<sup>−</sup>/NKX6.1<sup>+</sup>) with an undefined role in pancreatic cell fate. This novel population was enriched using our recently established protocol, allowing their reorganization in three-dimensional (3D) structures. Since NKX6.1 induction in MPCs can direct them to endocrine and/or ductal cells in humans, we examined the coexpression of endocrine and ductal markers. We found that the expression of the pancreatic endocrine progenitor markers chromogranin A (CHGA) and neurogenin 3 (NGN3) was not detected in the NKX6.1<sup>+</sup> 3D structures, while few structures were positive for NKX2.2, another endocrine progenitor marker, thereby shedding light on the origin of this novel population and its role in pancreatic endocrine development. Furthermore, SOX9 was highly expressed in the 3D structures, but cytokeratin 19, a main ductal marker, was not detected in these structures.</p><h3>Conclusions</h3><p dir="ltr">These data support the existence of two independent NKX6.1<sup>+</sup> MPC populations during human pancreatic development and the novel PDX1<sup>−</sup>/NKX6.1<sup>+</sup> population may be involved in a unique trajectory to generate β cells in humans.</p><h2>Other Information</h2><p dir="ltr">Published in: Stem Cell Research & Therapy<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="https://dx.doi.org/10.1186/s13287-018-0834-0" target="_blank">https://dx.doi.org/10.1186/s13287-018-0834-0</a></p>2018-04-03T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s13287-018-0834-0https://figshare.com/articles/journal_contribution/Differentiation_of_human_pluripotent_stem_cells_into_two_distinct_NKX6_1_populations_of_pancreatic_progenitors/25921105CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259211052018-04-03T03:00:00Z |
| spellingShingle | Differentiation of human pluripotent stem cells into two distinct NKX6.1 populations of pancreatic progenitors Idil I. Aigha (14913774) Biomedical and clinical sciences Medical biotechnology hESCs hiPSCs Pancreatic development Transcription factors Pancreatic progenitors β cells |
| status_str | publishedVersion |
| title | Differentiation of human pluripotent stem cells into two distinct NKX6.1 populations of pancreatic progenitors |
| title_full | Differentiation of human pluripotent stem cells into two distinct NKX6.1 populations of pancreatic progenitors |
| title_fullStr | Differentiation of human pluripotent stem cells into two distinct NKX6.1 populations of pancreatic progenitors |
| title_full_unstemmed | Differentiation of human pluripotent stem cells into two distinct NKX6.1 populations of pancreatic progenitors |
| title_short | Differentiation of human pluripotent stem cells into two distinct NKX6.1 populations of pancreatic progenitors |
| title_sort | Differentiation of human pluripotent stem cells into two distinct NKX6.1 populations of pancreatic progenitors |
| topic | Biomedical and clinical sciences Medical biotechnology hESCs hiPSCs Pancreatic development Transcription factors Pancreatic progenitors β cells |