Identification of Meibomian gland stem cell populations and mechanisms of aging

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 () and Sarah E. Millar ()
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Xuming Zhu: Icahn School of Medicine at Mount Sinai
Mingang Xu: Icahn School of Medicine at Mount Sinai
Celine Portal: Johns Hopkins University School of Medicine
Yvonne Lin: Johns Hopkins University School of Medicine
Alyssa Ferdinand: Icahn School of Medicine at Mount Sinai
Tien Peng: University of California San Francisco
Edward E. Morrisey: Perelman School of Medicine at the University of Pennsylvania
Andrzej A. Dlugosz: University of Michigan Medical School
Joseph M. Castellano: Icahn School of Medicine at Mount Sinai
Vivian Lee: Perelman School of Medicine at the University of Pennsylvania
John T. Seykora: Perelman School of Medicine at the University of Pennsylvania
Sunny Y. Wong: University of Michigan Medical School
Carlo Iomini: Johns Hopkins University School of Medicine
Sarah E. Millar: Icahn School of Medicine at Mount Sinai

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-56907-6

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