Development of lacrimal gland organoids from iPSC derived multizonal ocular cells
Lacrimal gland plays a vital role in maintaining the health and function of the ocular surface. Dysfunction of the gland leads to disruption of ocular surface homeostasis and can lead to severe outcomes. Approaches evolving through regenerative medicine have recently gained importance to restore the...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.1058846/full |
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| author | Melis Asal Melis Asal Gamze Koçak Gamze Koçak Vedat Sarı Vedat Sarı Tuba Reçber Emirhan Nemutlu Canan Aslı Utine Canan Aslı Utine Sinan Güven Sinan Güven Sinan Güven |
| author_facet | Melis Asal Melis Asal Gamze Koçak Gamze Koçak Vedat Sarı Vedat Sarı Tuba Reçber Emirhan Nemutlu Canan Aslı Utine Canan Aslı Utine Sinan Güven Sinan Güven Sinan Güven |
| author_sort | Melis Asal |
| collection | DOAJ |
| description | Lacrimal gland plays a vital role in maintaining the health and function of the ocular surface. Dysfunction of the gland leads to disruption of ocular surface homeostasis and can lead to severe outcomes. Approaches evolving through regenerative medicine have recently gained importance to restore the function of the gland. Using human induced pluripotent stem cells (iPSCs), we generated functional in vitro lacrimal gland organoids by adopting the multi zonal ocular differentiation approach. We differentiated human iPSCs and confirmed commitment to neuro ectodermal lineage. Then we identified emergence of mesenchymal and epithelial lacrimal gland progenitor cells by the third week of differentiation. Differentiated progenitors underwent branching morphogenesis in the following weeks, typical of lacrimal gland development. We were able to confirm the presence of lacrimal gland specific acinar, ductal, and myoepithelial cells and structures during weeks 4–7. Further on, we demonstrated the role of miR-205 in regulation of the lacrimal gland organoid development by monitoring miR-205 and FGF10 mRNA levels throughout the differentiation process. In addition, we assessed the functionality of the organoids using the β-Hexosaminidase assay, confirming the secretory function of lacrimal organoids. Finally, metabolomics analysis revealed a shift from amino acid metabolism to lipid metabolism in differentiated organoids. These functional, tear proteins secreting human lacrimal gland organoids harbor a great potential for the improvement of existing treatment options of lacrimal gland dysfunction and can serve as a platform to study human lacrimal gland development and morphogenesis. |
| first_indexed | 2024-04-11T01:02:03Z |
| format | Article |
| id | doaj.art-6c95135553f04e268f0bc768e5847264 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-11T01:02:03Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-6c95135553f04e268f0bc768e58472642023-01-04T15:37:44ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-01-011010.3389/fcell.2022.10588461058846Development of lacrimal gland organoids from iPSC derived multizonal ocular cellsMelis Asal0Melis Asal1Gamze Koçak2Gamze Koçak3Vedat Sarı4Vedat Sarı5Tuba Reçber6Emirhan Nemutlu7Canan Aslı Utine8Canan Aslı Utine9Sinan Güven10Sinan Güven11Sinan Güven12Izmir Biomedicine and Genome Center, Izmir, TurkeyIzmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, TurkeyIzmir Biomedicine and Genome Center, Izmir, TurkeyIzmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, TurkeyIzmir Biomedicine and Genome Center, Izmir, TurkeyIzmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, TurkeyDepartment of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, TurkeyDepartment of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, TurkeyIzmir Biomedicine and Genome Center, Izmir, TurkeyDepartment of Ophthalmology, Dokuz Eylül University Hospital, Dokuz Eylül University, Izmir, TurkeyIzmir Biomedicine and Genome Center, Izmir, TurkeyIzmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, TurkeyDepartment of Medical Biology and Genetics, Faculty of Medicine, Dokuz Eylül University, Izmir, TurkeyLacrimal gland plays a vital role in maintaining the health and function of the ocular surface. Dysfunction of the gland leads to disruption of ocular surface homeostasis and can lead to severe outcomes. Approaches evolving through regenerative medicine have recently gained importance to restore the function of the gland. Using human induced pluripotent stem cells (iPSCs), we generated functional in vitro lacrimal gland organoids by adopting the multi zonal ocular differentiation approach. We differentiated human iPSCs and confirmed commitment to neuro ectodermal lineage. Then we identified emergence of mesenchymal and epithelial lacrimal gland progenitor cells by the third week of differentiation. Differentiated progenitors underwent branching morphogenesis in the following weeks, typical of lacrimal gland development. We were able to confirm the presence of lacrimal gland specific acinar, ductal, and myoepithelial cells and structures during weeks 4–7. Further on, we demonstrated the role of miR-205 in regulation of the lacrimal gland organoid development by monitoring miR-205 and FGF10 mRNA levels throughout the differentiation process. In addition, we assessed the functionality of the organoids using the β-Hexosaminidase assay, confirming the secretory function of lacrimal organoids. Finally, metabolomics analysis revealed a shift from amino acid metabolism to lipid metabolism in differentiated organoids. These functional, tear proteins secreting human lacrimal gland organoids harbor a great potential for the improvement of existing treatment options of lacrimal gland dysfunction and can serve as a platform to study human lacrimal gland development and morphogenesis.https://www.frontiersin.org/articles/10.3389/fcell.2022.1058846/fullinduced pluripotent stem cellsdifferentiationdevelopmental biologystem celllacrimal glandorganoid |
| spellingShingle | Melis Asal Melis Asal Gamze Koçak Gamze Koçak Vedat Sarı Vedat Sarı Tuba Reçber Emirhan Nemutlu Canan Aslı Utine Canan Aslı Utine Sinan Güven Sinan Güven Sinan Güven Development of lacrimal gland organoids from iPSC derived multizonal ocular cells Frontiers in Cell and Developmental Biology induced pluripotent stem cells differentiation developmental biology stem cell lacrimal gland organoid |
| title | Development of lacrimal gland organoids from iPSC derived multizonal ocular cells |
| title_full | Development of lacrimal gland organoids from iPSC derived multizonal ocular cells |
| title_fullStr | Development of lacrimal gland organoids from iPSC derived multizonal ocular cells |
| title_full_unstemmed | Development of lacrimal gland organoids from iPSC derived multizonal ocular cells |
| title_short | Development of lacrimal gland organoids from iPSC derived multizonal ocular cells |
| title_sort | development of lacrimal gland organoids from ipsc derived multizonal ocular cells |
| topic | induced pluripotent stem cells differentiation developmental biology stem cell lacrimal gland organoid |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.1058846/full |
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