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KROX20-Notch1 Network Transcriptionally Regulates Meibomian Gland Stem Cells for Its Development and Homeostasis [ChIP-Seq]

ABSTRACT: Meibomian gland dysfunction is the leading cause of Evaporative Dry Eye Disease (EDED), and accounts for approximately 90% of dry eye disease cases worldwide. The transcription factor Krox20 has been shown to mark stem cells that play a critical role in Meibomian gland (MG) development and homeostasis, however, the molecular mechanisms underlying these processes are not well understood. In this report, we used multiple Krox20 lineage tracing and ablation studies to investigate the process that governs lineage commitment during MG morphogenesis and homeostasis. Krox20 marks MG stem/progenitor cell pools, and it regulates cellular contributions to the glands, as loss of Krox20 leads to MG atrophy, while its overexpression results in MG enlargement. We also found that Notch1 signaling is regulated by KROX20 and that ablation of the Notch1 gene in KROX20-expressing cells leads to MG atrophy, while Notch1 overexpression partially rescues MG atrophy caused by the loss of Krox20. Together, these results reveal a critical KROX20-Notch1 regulatory pathway in MG stem/progenitor cells. Activation of Notch1 signaling may offer a novel approach to preventing and treating EDED caused by the depletion of the MG stem cell pool that can occur with aging.

ORGANISM(S): Homo sapiens

PROVIDER: GSE289069 | GEO | 2025/11/01

REPOSITORIES: GEO

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KROX20-Notch1 Network Transcriptionally Regulates Meibomian Gland Stem Cells for Its Development and Homeostasis

Project description:Meibomian gland dysfunction is the leading cause of Evaporative Dry Eye Disease (EDED), and accounts for approximately 90% of dry eye disease cases worldwide. The transcription factor Krox20 has been shown to mark stem cells that play a critical role in Meibomian gland (MG) development and homeostasis, however, the molecular mechanisms underlying these processes are not well understood. In this report, we used multiple Krox20 lineage tracing and ablation studies to investigate the process that governs lineage commitment during MG morphogenesis and homeostasis. Krox20 marks MG stem/progenitor cell pools, and it regulates cellular contributions to the glands, as loss of Krox20 leads to MG atrophy, while its overexpression results in MG enlargement. We also found that Notch1 signaling is regulated by KROX20 and that ablation of the Notch1 gene in KROX20-expressing cells leads to MG atrophy, while Notch1 overexpression partially rescues MG atrophy caused by the loss of Krox20. Together, these results reveal a critical KROX20-Notch1 regulatory pathway in MG stem/progenitor cells. Activation of Notch1 signaling may offer a novel approach to preventing and treating EDED caused by the depletion of the MG stem cell pool that can occur with aging.

2025-11-01 | GSE288952 | GEO

scRNA-seq reveals the impact of dysfunction on meibomian gland population dynamics

Project description:While meibomian gland dysfunction (MGD) is widely recognized as a major cause of evaporative dry eye disease, little is known about normal gland differentiation and lipid synthesis or the mechanism underlying gland atrophy and abnormal lipid secretion. In this study, we used single-cell and spatial transcriptomics to probe changes in cell composition, differentiation, and gene expression associated with two murine models of MGD: age-related gland atrophy in wild-type mice and altered meibum quality in acyl-CoA wax alcohol acyltransferase 2 (Awat2) knockout (KO) mice. We identified the stratified expression of lipogenic genes during meibocyte differentiation, which may control the progressive synthesis of meibum lipids; an age-related decrease in meibocytes; and increased immune cell infiltration. Additionally, we detected unique immune cell populations in the Awat2 KO mouse suggesting the activation of psoriasis-like, inflammatory pathways associated with the synthesis of altered meibum quality causing ductal dilation and hyperplasia of the duct. Together these findings support novel mechanism controlling gland function and dysfunction.

2025-01-07 | GSE261036 | GEO

KROX20-Notch1 Network Transcriptionally Regulates Meibomian Gland Stem Cells for Its Development and Homeostasis

Project description:KROX20-Notch1 Network Transcriptionally Regulates Meibomian Gland Stem Cells for Its Development and Homeostasis

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KROX20-Notch1 Network Transcriptionally Regulates Meibomian Gland Stem Cells for Its Development and Homeostasis [ChIP-Seq]

Project description:KROX20-Notch1 Network Transcriptionally Regulates Meibomian Gland Stem Cells for Its Development and Homeostasis [ChIP-Seq]

| PRJNA1220984 | ENA

Dihydrotestosterone induced changes in gene expression in immortalized human meibomian gland epithelial cells

2011-03-31 | GSE18091 | GEO

Dihydrotestosterone induced changes in gene expression in immortalized human meibomian gland epithelial cells

Project description:Genome-wide analysis of dihydrotestosterone (DHT) induced changes in gene expression in immortalized human meibomian gland epithelial cells. Analysis of regulation of immortalized human meibomian gland epithelial cells by dihydrotestosterone at gene expression level. The hypothesis tested in the present study was that the androgen-eye interaction in ocular surface epithelial cells like meibomian gland cells is influenced by androgens through regulation of the expression of multiple genes. Results provide important information of the differential regulation of numerous genes in response to dihydrotestosterone incubation of immortalized human meibomian gland epithelial cells. Total RNA was obtained from immortalized human meibomian gland epithelial cells treated for 72 hours with 10 nM dihydrotestosterone (n=3) or vehicle (n=3). The RNA was then used with Illumina HumanHT-12 v3 Expression BeadChips to determine the effect of DHT on gene expression in an immortalized human meibomian epithelial cell line developed in our laboratory.

2011-03-31 | E-GEOD-18091 | biostudies-arrayexpress

Wild-type and Hsd3b6-deficient mouse meibomian gland transcriptome

Project description:To dissect molecular mechanisms underlying Hsd3b6−/−meibomian gland phenotypes, we performed RNA-sequencing (RNA-seq) analysis using fluorescence-activated cell sorting (FACS)-purified meibomian gland cells. RNA-seq analysis was performed using FACS-purified Itgav(+);CD45(−) meibomian gland acinar cells from wildtype and Hsd3b6−/−mice.As revealed by gene ontology (GO) enrichment analysis, cells sorted from Hsd3b6−/−mice show increased expression of inflammation-related genes. On the other hand, downregulated genes exhibit the highest enrichment score for the GO term related to “regulation of anatomical structure morphogenesis”, a signature accounting for the phenotype of the meibomian gland atrophy of Hsd3b6−/− mice.

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Project description:Hyperlipidemia can induce the dysfunction of meibomian gland (MG) in mice, which may be affected by circadian rhythm. However, the underlying mechanism remains unclear. In this study, we exposed the hyperlipidemic mice model induced by four months feeding of high-fat diet to the regular light-dark cycles for two weeks. Then, phenotypic observation and RNA-seq of MG in experimental mice were performed to investigate the effect and transcriptional changes of hyperlipidemia and circadian rhythm on MG dysfunction. As a result, several significantly expressed genes and enriched pathways were identified to be associated with MG dysfunction in hyperlipidemic mice under circadian rhythms. High fat diet can not only bring hyperlipidemia, but also cause meibomian gland dysfunction, which is affected by rhythm genes. These data can provide us with a deeper understanding of the outcomes of MG altered by daily nutritional challenge.

2023-01-01 | GSE185613 | GEO

Growth factor influence on the gene expression profile of human meibomian gland epithelial cells

Project description:Analysis of growth factor influence on immortalized human meibomian gland epithelial cells at gene expression level. Growth factors play a critical role in the proliferation and differentiation of sebaceous gland epithelial cells. Given that the meibomian gland is a large sebaceous gland, we hypothesize that growth factors exert analogous effects on human meibomian gland epithelial cells. Results provide important information of the response of human meibomian gland epithelial cells to epidermal growth factor (EGF), bovine pituitary extract (BPE), and both, such as up- or down- regulated genes involved in lipid metabolic process and cell cycle.

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