PAX6-dependent differentiation landscape of ocular surface epithelium via single-cell RNA sequencing in hiPSC-derived ocular developmental organoid
Abstract During eye development, surface ectoderm cells that express PAX6 differentiate into corneal, limbal and conjunctival epithelia. However, several aspects of this differentiation process -- such as the developmental origin of the limbal epithelium and the mechanisms that underlie PAX6-mediate...
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| Format: | Article |
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Nature Portfolio
2025-08-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08643-2 |
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| author | Rei Kamuro Masahito Yoshihara Susumu Hara Takahiro Nemoto Laura Howard Ai Honda Ayano Yamamoto Toru Takigawa Susumu Sakimoto Koichi Baba Andrew J. Quantock Kohji Nishida |
| author_facet | Rei Kamuro Masahito Yoshihara Susumu Hara Takahiro Nemoto Laura Howard Ai Honda Ayano Yamamoto Toru Takigawa Susumu Sakimoto Koichi Baba Andrew J. Quantock Kohji Nishida |
| author_sort | Rei Kamuro |
| collection | DOAJ |
| description | Abstract During eye development, surface ectoderm cells that express PAX6 differentiate into corneal, limbal and conjunctival epithelia. However, several aspects of this differentiation process -- such as the developmental origin of the limbal epithelium and the mechanisms that underlie PAX6-mediated lineage specification -- are not properly understood. To explore these issues, we used single-cell RNA sequencing to study ocular surface epithelial cells derived from human induced pluripotent stem cells. Our analysis reveals that the corneal and conjunctival epithelial cell lineages originate from the surface ectoderm, and that the conjunctival lineage contributes to limbal epithelial cell populations. We also show that primordial conjunctival epithelial cells express limbal epithelial markers before lineage bifurcation. Finally, the activity and expression of PAX6 are highest in corneal epithelial cells, followed by those of the limbal epithelium and conjunctival epithelium, suggesting that lineage-specific differentiation is regulated by levels of PAX6 activity. These findings provide deeper understanding of the early-stage human ocular surface development. |
| format | Article |
| id | doaj-art-2e2daf854f2d4a5fb1c5830663c6f0a4 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-2e2daf854f2d4a5fb1c5830663c6f0a42025-08-20T03:46:21ZengNature PortfolioCommunications Biology2399-36422025-08-018111610.1038/s42003-025-08643-2PAX6-dependent differentiation landscape of ocular surface epithelium via single-cell RNA sequencing in hiPSC-derived ocular developmental organoidRei Kamuro0Masahito Yoshihara1Susumu Hara2Takahiro Nemoto3Laura Howard4Ai Honda5Ayano Yamamoto6Toru Takigawa7Susumu Sakimoto8Koichi Baba9Andrew J. Quantock10Kohji Nishida11Department of Ophthalmology, The University of Osaka Graduate School of MedicinePremium Research Institute for Human Metaverse Medicine (WPI-PRIMe), The University of Osaka, SuitaDepartment of Ophthalmology, The University of Osaka Graduate School of MedicinePremium Research Institute for Human Metaverse Medicine (WPI-PRIMe), The University of Osaka, SuitaSchool of Optometry and Vision Sciences, Cardiff UniversityDepartment of Ophthalmology, The University of Osaka Graduate School of MedicineDepartment of Ophthalmology, The University of Osaka Graduate School of MedicineDepartment of Ophthalmology, The University of Osaka Graduate School of MedicineDepartment of Ophthalmology, The University of Osaka Graduate School of MedicineDepartment of Ophthalmology, The University of Osaka Graduate School of MedicineSchool of Optometry and Vision Sciences, Cardiff UniversityDepartment of Ophthalmology, The University of Osaka Graduate School of MedicineAbstract During eye development, surface ectoderm cells that express PAX6 differentiate into corneal, limbal and conjunctival epithelia. However, several aspects of this differentiation process -- such as the developmental origin of the limbal epithelium and the mechanisms that underlie PAX6-mediated lineage specification -- are not properly understood. To explore these issues, we used single-cell RNA sequencing to study ocular surface epithelial cells derived from human induced pluripotent stem cells. Our analysis reveals that the corneal and conjunctival epithelial cell lineages originate from the surface ectoderm, and that the conjunctival lineage contributes to limbal epithelial cell populations. We also show that primordial conjunctival epithelial cells express limbal epithelial markers before lineage bifurcation. Finally, the activity and expression of PAX6 are highest in corneal epithelial cells, followed by those of the limbal epithelium and conjunctival epithelium, suggesting that lineage-specific differentiation is regulated by levels of PAX6 activity. These findings provide deeper understanding of the early-stage human ocular surface development.https://doi.org/10.1038/s42003-025-08643-2 |
| spellingShingle | Rei Kamuro Masahito Yoshihara Susumu Hara Takahiro Nemoto Laura Howard Ai Honda Ayano Yamamoto Toru Takigawa Susumu Sakimoto Koichi Baba Andrew J. Quantock Kohji Nishida PAX6-dependent differentiation landscape of ocular surface epithelium via single-cell RNA sequencing in hiPSC-derived ocular developmental organoid Communications Biology |
| title | PAX6-dependent differentiation landscape of ocular surface epithelium via single-cell RNA sequencing in hiPSC-derived ocular developmental organoid |
| title_full | PAX6-dependent differentiation landscape of ocular surface epithelium via single-cell RNA sequencing in hiPSC-derived ocular developmental organoid |
| title_fullStr | PAX6-dependent differentiation landscape of ocular surface epithelium via single-cell RNA sequencing in hiPSC-derived ocular developmental organoid |
| title_full_unstemmed | PAX6-dependent differentiation landscape of ocular surface epithelium via single-cell RNA sequencing in hiPSC-derived ocular developmental organoid |
| title_short | PAX6-dependent differentiation landscape of ocular surface epithelium via single-cell RNA sequencing in hiPSC-derived ocular developmental organoid |
| title_sort | pax6 dependent differentiation landscape of ocular surface epithelium via single cell rna sequencing in hipsc derived ocular developmental organoid |
| url | https://doi.org/10.1038/s42003-025-08643-2 |
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