Identification of Meibomian gland stem cell populations and mechanisms of aging
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.
Authors
- Joseph M. Castellano (ORCID: https://orcid.org/0000-0002-8026-6292)
- Xuming Zhu (ORCID: https://orcid.org/0000-0003-1148-4162)
- Sarah E. Millar (ORCID: https://orcid.org/0000-0001-8792-6890)
- Andrzej A. Dlugosz (ORCID: https://orcid.org/0000-0002-9791-3257)
- John T. Seykora (ORCID: https://orcid.org/0000-0003-0383-031X)
- Edward E. Morrisey (ORCID: https://orcid.org/0000-0001-5785-1939)
- Tien Peng
- Carlo Iomini (ORCID: https://orcid.org/0000-0001-6483-9540)
- Céline Portal (ORCID: https://orcid.org/0000-0002-1862-0166)
- Sunny Y. Wong (ORCID: https://orcid.org/0000-0002-0222-2681)
- Vivian Lee (ORCID: https://orcid.org/0000-0002-4470-0143)
- Mingang Xu (ORCID: https://orcid.org/0000-0001-7357-4038)
- Yvonne G. Lin (ORCID: https://orcid.org/0000-0002-4598-1696)
- Alyssa Ferdinand
Institutions
- Centre National de la Recherche Scientifique (FR)
- Allen Institute for Brain Science (US)
- Institut de la Vision (FR)
- Johns Hopkins University (US)
- Inserm (FR)
- University of California, San Francisco (US)
- University of Michigan (US)
- Johns Hopkins Medicine (US)
- Sorbonne Université (FR)
- Tisch Hospital (US)
- University of Pennsylvania (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-02-15
- DOI
- https://doi.org/10.1038/s41467-025-56907-6
- Citations
- 16
- Primary Topic
- Ocular Surface and Contact Lens
- Type
- article
- Field-Weighted Citation Impact
- 30.06
Funders
- University of Pennsylvania
- National Institutes of Health
- Penn Skin Biology and Diseases Resource-based Center, University of Pennsylvania
- National Eye Institute
- National Cancer Institute
- National Institute of Arthritis and Musculoskeletal and Skin Diseases