Human meibomian gland organoids to study epithelial homeostasis and dysfunction
Meibomian glands (MGs) are holocrine glands that secrete lipids to maintain the homeostasis of ocular surface, and their dysfunction leads to dry eye disease. Herein, we established long-term 3D organoid culture for murine and human MGs, which retained the cell lineages and lipid-producing ability. The organoids mimicked the drug treatment responses and generated functional MGs after orthotopic transplantation. Inspired by organoid cultures, we found FGF10 eye drops could rescue all-trans retinoic acid-induced MG dysfunction in mice. Besides, nicotinamide uniquely hampered the human MG organoid expansion by inhibiting FGF10 signaling. Single-cell atlas and lipidome not only aligned the delineated cell types and featured lipids between human MGs and organoids, but highlighting MAPK signaling inhibition enhanced acinar cell differentiation and functional maturation of MG organoids. In summary, this study established an organoid platform to explore epithelial homeostasis and dysfunction of MGs, facilitating drug development and regenerative medicine for dry eye disease.
Authors
- Qihua Le (ORCID: https://orcid.org/0000-0001-7655-3101)
- Bing Tian Zhao (ORCID: https://orcid.org/0000-0001-9891-3569)
- Xichen Wan (ORCID: https://orcid.org/0000-0002-4550-0178)
- Jinsong Wei (ORCID: https://orcid.org/0000-0003-2343-9705)
- Chuyue Yu (ORCID: https://orcid.org/0000-0002-3286-3199)
- Jiaxu Hong
- Chen Zhao (ORCID: https://orcid.org/0000-0001-6253-7522)
- Xingru Wu (ORCID: https://orcid.org/0000-0002-4341-6335)
- Xujiao Zhou (ORCID: https://orcid.org/0000-0002-9719-4889)
- Yiming Zhang (ORCID: https://orcid.org/0000-0003-1000-9108)
- Xiaoye Wang (ORCID: https://orcid.org/0000-0003-3540-0277)
- Xinghuai Sun (ORCID: https://orcid.org/0000-0002-4440-1389)
- Zhaoting Xu (ORCID: https://orcid.org/0009-0004-3295-4869)
- Dan Wu (ORCID: https://orcid.org/0009-0004-0859-0006)
- Jianjiang Xu
- Yan‐jun Mi
- Xingtao Zhou
Institutions
- Nanchang University (CN)
- Shanghai Eye Disease Prevention & Treatment Center (CN)
- First Affiliated Hospital of Jiangxi Medical College (CN)
- Eye & ENT Hospital of Fudan University (CN)
- Shanghai Cell Therapy Research Institute (CN)
- Children's Hospital of Fudan University (CN)
- Viva Biotech (China) (CN)
- First Affiliated Hospital of Nanchang University (CN)
- National Center for Genetic Engineering and Biotechnology (TH)
Publication Details
- Journal
- Protein & Cell
- Published
- 2025-11-07
- DOI
- https://doi.org/10.1093/procel/pwaf095
- Primary Topic
- Ocular Surface and Contact Lens
- Type
- article
- Field-Weighted Citation Impact
- 0.00