Epithelial stem cell homeostasis in Meibomian gland development, dysfunction, and dry eye disease
Dry eye disease affects over 16 million adults in the US, and the majority of cases are due to Meibomian gland dysfunction. Unfortunately, the identity of the stem cells involved in Meibomian gland development and homeostasis is not well elucidated. Here, we report that loss of Krox20, a zinc finger...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2021-10-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.151078 |
| _version_ | 1811226996318928896 |
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| author | Edem Tchegnon Chung-Ping Liao Elnaz Ghotbi Tracey Shipman Yong Wang Renee M. McKay Lu Q. Le |
| author_facet | Edem Tchegnon Chung-Ping Liao Elnaz Ghotbi Tracey Shipman Yong Wang Renee M. McKay Lu Q. Le |
| author_sort | Edem Tchegnon |
| collection | DOAJ |
| description | Dry eye disease affects over 16 million adults in the US, and the majority of cases are due to Meibomian gland dysfunction. Unfortunately, the identity of the stem cells involved in Meibomian gland development and homeostasis is not well elucidated. Here, we report that loss of Krox20, a zinc finger transcription factor involved in the development of ectoderm-derived tissues, or deletion of KROX20-expressing epithelial cells disrupted Meibomian gland formation and homeostasis, leading to dry eye disease secondary to Meibomian gland dysfunction. Ablation of Krox20-lineage cells in adult mice also resulted in dry eye disease, implicating Krox20 in homeostasis of the mature Meibomian gland. Lineage-tracing and expression analyses revealed a restricted KROX20 expression pattern in the ductal areas of the Meibomian gland, although Krox20-lineage cells generate the full, mature Meibomian gland. This suggests that KROX20 marks a stem/progenitor cell population that differentiates to generate the entire Meibomian gland. Our Krox20 mouse models provide a powerful system that delineated the identity of stem cells required for Meibomian gland development and homeostasis and can be used to investigate the factors underlying these processes. They are also robust models of Meibomian gland dysfunction–related dry eye disease, with a potential for use in preclinical therapeutic screening. |
| first_indexed | 2024-04-12T09:33:59Z |
| format | Article |
| id | doaj.art-d956a931a5de4fc7b40d381a8a33922c |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-04-12T09:33:59Z |
| publishDate | 2021-10-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-d956a931a5de4fc7b40d381a8a33922c2022-12-22T03:38:17ZengAmerican Society for Clinical investigationJCI Insight2379-37082021-10-01620Epithelial stem cell homeostasis in Meibomian gland development, dysfunction, and dry eye diseaseEdem TchegnonChung-Ping LiaoElnaz GhotbiTracey ShipmanYong WangRenee M. McKayLu Q. LeDry eye disease affects over 16 million adults in the US, and the majority of cases are due to Meibomian gland dysfunction. Unfortunately, the identity of the stem cells involved in Meibomian gland development and homeostasis is not well elucidated. Here, we report that loss of Krox20, a zinc finger transcription factor involved in the development of ectoderm-derived tissues, or deletion of KROX20-expressing epithelial cells disrupted Meibomian gland formation and homeostasis, leading to dry eye disease secondary to Meibomian gland dysfunction. Ablation of Krox20-lineage cells in adult mice also resulted in dry eye disease, implicating Krox20 in homeostasis of the mature Meibomian gland. Lineage-tracing and expression analyses revealed a restricted KROX20 expression pattern in the ductal areas of the Meibomian gland, although Krox20-lineage cells generate the full, mature Meibomian gland. This suggests that KROX20 marks a stem/progenitor cell population that differentiates to generate the entire Meibomian gland. Our Krox20 mouse models provide a powerful system that delineated the identity of stem cells required for Meibomian gland development and homeostasis and can be used to investigate the factors underlying these processes. They are also robust models of Meibomian gland dysfunction–related dry eye disease, with a potential for use in preclinical therapeutic screening.https://doi.org/10.1172/jci.insight.151078Ophthalmology |
| spellingShingle | Edem Tchegnon Chung-Ping Liao Elnaz Ghotbi Tracey Shipman Yong Wang Renee M. McKay Lu Q. Le Epithelial stem cell homeostasis in Meibomian gland development, dysfunction, and dry eye disease JCI Insight Ophthalmology |
| title | Epithelial stem cell homeostasis in Meibomian gland development, dysfunction, and dry eye disease |
| title_full | Epithelial stem cell homeostasis in Meibomian gland development, dysfunction, and dry eye disease |
| title_fullStr | Epithelial stem cell homeostasis in Meibomian gland development, dysfunction, and dry eye disease |
| title_full_unstemmed | Epithelial stem cell homeostasis in Meibomian gland development, dysfunction, and dry eye disease |
| title_short | Epithelial stem cell homeostasis in Meibomian gland development, dysfunction, and dry eye disease |
| title_sort | epithelial stem cell homeostasis in meibomian gland development dysfunction and dry eye disease |
| topic | Ophthalmology |
| url | https://doi.org/10.1172/jci.insight.151078 |
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