Identification of Meibomian gland stem cell populations and mechanisms of aging
Abstract Meibomian glands secrete lipid-rich meibum, which prevents tear evaporation. Aging-related Meibomian gland shrinkage may result in part from stem cell exhaustion and is associated with evaporative dry eye disease, a common condition lacking effective treatment. The identities and niche of M...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56907-6 |
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| author | Xuming Zhu Mingang Xu Celine Portal Yvonne Lin Alyssa Ferdinand Tien Peng Edward E. Morrisey Andrzej A. Dlugosz Joseph M. Castellano Vivian Lee John T. Seykora Sunny Y. Wong Carlo Iomini Sarah E. Millar |
| author_facet | Xuming Zhu Mingang Xu Celine Portal Yvonne Lin Alyssa Ferdinand Tien Peng Edward E. Morrisey Andrzej A. Dlugosz Joseph M. Castellano Vivian Lee John T. Seykora Sunny Y. Wong Carlo Iomini Sarah E. Millar |
| author_sort | Xuming Zhu |
| collection | DOAJ |
| description | Abstract Meibomian glands secrete lipid-rich meibum, which prevents tear evaporation. Aging-related Meibomian gland shrinkage may result in part from stem cell exhaustion and is associated with evaporative dry eye disease, a common condition lacking effective treatment. The identities and niche of Meibomian gland stem cells and the signals controlling their activity are poorly defined. Using snRNA-seq, in vivo lineage tracing, ex vivo live imaging, and genetic studies in mice, we identify markers for stem cell populations that maintain distinct regions of the gland and uncover Hedgehog (Hh) signaling as a key regulator of stem cell proliferation. Consistent with this, we show that human Meibomian gland carcinoma exhibits increased Hh signaling. Aged glands display decreased Hh and EGF signaling, deficient innervation, and loss of collagen I in niche fibroblasts, indicating that alterations in both glandular epithelial cells and their surrounding microenvironment contribute to age-related degeneration. These findings suggest new approaches to treat aging-associated Meibomian gland loss. |
| format | Article |
| id | doaj-art-a2d01c780f084e6f90e2c6c00a72a67c |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a2d01c780f084e6f90e2c6c00a72a67c2025-08-20T02:12:58ZengNature PortfolioNature Communications2041-17232025-02-0116111910.1038/s41467-025-56907-6Identification of Meibomian gland stem cell populations and mechanisms of agingXuming Zhu0Mingang Xu1Celine Portal2Yvonne Lin3Alyssa Ferdinand4Tien Peng5Edward E. Morrisey6Andrzej A. Dlugosz7Joseph M. Castellano8Vivian Lee9John T. Seykora10Sunny Y. Wong11Carlo Iomini12Sarah E. Millar13Black Family Stem Cell Institute, Icahn School of Medicine at Mount SinaiBlack Family Stem Cell Institute, Icahn School of Medicine at Mount SinaiDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of MedicineDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of MedicineBlack Family Stem Cell Institute, Icahn School of Medicine at Mount SinaiDepartment of Medicine, University of California San FranciscoDepartment of Medicine, Perelman School of Medicine at the University of PennsylvaniaDepartment of Dermatology, University of Michigan Medical SchoolBlack Family Stem Cell Institute, Icahn School of Medicine at Mount SinaiDepartment of Ophthalmology, Perelman School of Medicine at the University of PennsylvaniaDepartment of Dermatology, Perelman School of Medicine at the University of PennsylvaniaDepartment of Dermatology, University of Michigan Medical SchoolDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of MedicineBlack Family Stem Cell Institute, Icahn School of Medicine at Mount SinaiAbstract Meibomian glands secrete lipid-rich meibum, which prevents tear evaporation. Aging-related Meibomian gland shrinkage may result in part from stem cell exhaustion and is associated with evaporative dry eye disease, a common condition lacking effective treatment. The identities and niche of Meibomian gland stem cells and the signals controlling their activity are poorly defined. Using snRNA-seq, in vivo lineage tracing, ex vivo live imaging, and genetic studies in mice, we identify markers for stem cell populations that maintain distinct regions of the gland and uncover Hedgehog (Hh) signaling as a key regulator of stem cell proliferation. Consistent with this, we show that human Meibomian gland carcinoma exhibits increased Hh signaling. Aged glands display decreased Hh and EGF signaling, deficient innervation, and loss of collagen I in niche fibroblasts, indicating that alterations in both glandular epithelial cells and their surrounding microenvironment contribute to age-related degeneration. These findings suggest new approaches to treat aging-associated Meibomian gland loss.https://doi.org/10.1038/s41467-025-56907-6 |
| spellingShingle | Xuming Zhu Mingang Xu Celine Portal Yvonne Lin Alyssa Ferdinand Tien Peng Edward E. Morrisey Andrzej A. Dlugosz Joseph M. Castellano Vivian Lee John T. Seykora Sunny Y. Wong Carlo Iomini Sarah E. Millar Identification of Meibomian gland stem cell populations and mechanisms of aging Nature Communications |
| title | Identification of Meibomian gland stem cell populations and mechanisms of aging |
| title_full | Identification of Meibomian gland stem cell populations and mechanisms of aging |
| title_fullStr | Identification of Meibomian gland stem cell populations and mechanisms of aging |
| title_full_unstemmed | Identification of Meibomian gland stem cell populations and mechanisms of aging |
| title_short | Identification of Meibomian gland stem cell populations and mechanisms of aging |
| title_sort | identification of meibomian gland stem cell populations and mechanisms of aging |
| url | https://doi.org/10.1038/s41467-025-56907-6 |
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