Gene expression profle at single cell level of lacrimal gland
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE280211 | GEO | 2025/05/08
REPOSITORIES: GEO
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Project description:The lacrimal gland (LG) is the major source of aqueous tears, and insufficient LG secretion leads to aqueous-deficient dry eye (ADDE) disease. To provide a foundational description of LG's protein expression patterns, we prepared protein extracts of LGs from a wild-type and an ADDE mouse model and analyzed the proteome by quantitative mass spectrometry.
2025-04-18 | PXD060937 | Pride
Project description:Although tear replacement and anti-inflammatory treatments have been thoroughly investigated, a method to induce epithelial restoration is lacking. Here, we asked whether WNT signaling activation via an antibody-based WNT mimetic platform might activate lacrimal gland acinar cells and restore tear secretion. Transcriptional and cellular changes were investigated using single cell sequencing. In a mouse model of dry eye disease, and intra-lacrimal gland treatment with a WNT mimetic targeting FZD1, 2, and 7 reversed aqueous tear deficiency. After excretory duct ligation damage, WNT mimetic treatment promoted acinar cell restoration and increased detectable tear volume production. We demonstrate a role for WNT signaling in acinar cell proliferation, and scRNA-seq revealed that the WNT mimetic promotes pathway activation and proliferation in injury-induced states. Our findings extend the potential for WNT pathway activation via a ligand mimetic platform to lacrimal gland regeneration.
2025-06-10 | GSE295860 | GEO
Project description:Previous studies showed that loss of muscarinic parasympathetic input to the lacrimal gland (LG) leads to a dramatic reduction in tear secretion and profound changes to LG structure. In this study, we used DNA microarrays to examine the regulation of the gene expression of the genes for secretory function and organization of the LG. Long-Evans rats anesthetized with a mixture of ketamine/xylazine (80:10 mg/kg) underwent unilateral sectioning of the greater superficial petrosal nerve, the input to the pterygopalatine ganglion. After 7 days, tear secretion was measured, the animals were killed, and structural changes in the LG were examined by light microscopy. Total RNA from control and experimental LGs (n = 5) was used for DNA microarray analysis employing the U34A GeneChip. Control rat lacrimal gland samples representing a normal unoperated, a sham, and paired contralateral controls. Experimental LG samples representing paired and unpaired contralateral controls. Paired contralateral control LGs represent LG from the same animal, one side was operated and the other side unoperated.
2007-10-12 | E-GEOD-844 | biostudies-arrayexpress
Project description:In humans, the lacrimal gland produces the aqueous component of the tear film, which e.g. moistens and nourishes the ocular surface to maintain ophthalmic health. Decreased production of the aqueous component leads to the development of dry eye disease, which affects over 250 million people worldwide. Despite the impact on patients, the availability of primary human material to study underlying disease mechanisms is severely constrained. Here, we report the development of an immortalized human lacrimal gland epithelial cell line that improves accessibility to study the molecular pathogenesis-mechanisms of dry eye disease and link them to causal treatments.
2024-04-17 | GSE239464 | GEO
Project description:As an element of the lacrimal apparatus, the lacrimal gland (LG) produces the aqueous part of the tear film, which protects the eye surface. Therefore, a defective LG can lead to serious eyesight impairment. Up to now, little is known about LG morphogenesis and subsequent maturation. In this study, we delineated elements of the cellular and molecular events involved in LG formation by using three epithelial markers, namely aSMA, Krt14 andKrt19. While aSMA marked a restricted epithelial population of the terminal end buds (TEBs) in the forming LG, Krt14 was found in the whole embryonic LG epithelial basal cell layer. Interestingly, Krt19 specifically labelled the presumptive ductal domain and subsequently, the luminal cell layer. By combining these markers, the Fucci reporter mouse strain and genetic fate mapping of the Krt14+ population, we demonstrated that LG epithelium expansion is fueled by a patterned cell proliferation, and to a lesser extent by epithelial reorganization and possible mesenchymal-to-epithelial transition. We pointed out that this epithelial reorganization, which is associated with apoptosis, regulated the lumen formation. Finally, we showed that the Notch signalling inhibition prevented the ductal identity from setting, and leads to a LG covered by ectopic TEBs. Taken together our results bring a deeper understanding on LG morphogenesis, epithelial domain identity, and organ expansion.
2017-09-13 | GSE103743 | GEO
Project description:The transcriptional expression analysis of 17.5, 19.5 days embryonic lacrimal gland (LG), adult lacrimal gland, lacrimal gland stem cells (LGSCs) P2 cultured for 5, 7, 10, 14 days and LGSCs P6, P10, P20 cultured for 7 days, respectively.
2019-08-06 | GSE135398 | GEO
Project description:Tears are mainly secreted from the lacrimal gland under precise controls by autonomic neural response to external sensory and psychogenic emotional stimulation. Dynamic volume and compositional changes of tears may lead to development of dry eye disease. The role of sympathetic nerve system (SNS) in controlling tear secretion and the noradrenergic neural circuit projecting from brain to lacrimal gland remain unexplored. Here, we discovered the dense sympathetic innervation of mouse lacrimal gland and investigated its physiological role in regulating tear production. In response to dry eye stimuli, SNS became overactivated with high noradrenaline (NA) in the lacrimal gland. Using gain- and loss-of-functional approaches, including pharmacologic, surgical, chemogenetic manipulations, and genetic knockout mice of specific adrenergic receptors, we demonstrated that both SNS ablation and NA blockage markedly increased tear volume and alleviated dry eye diseases. Mechanistically, activation of SNS released NA to reduce tear secretion through binding to α1a-adrenergic receptor (Adra1a) that targeted mitochondrial Ucp2 in the acinar and myoepithelial cells of the lacrimal gland. Consequently, antagonization of NA and Ucp2 markedly increased tear secretion. Using a retrograde neuronal tracing technique in combination with physiologic experiments of tear reduction and hypersecretion, we identified a novel noradrenergic neural circuit projecting from the brain locus coeruleus to the lacrimal gland and the orchestrated controlling of parasympathetic and sympathetic nervous system for tear secretion. Together, our data define a novel NA-Adra1a-Ucp2 signaling pathway as a gatekeeper mechanism for controlling tear secretion from the lacrimal gland. These findings provide novel mechanistic insights into sympathetic role in tear secretion and potential therapeutic options for treatment of dry eye disease.
2025-05-08 | GSE224484 | GEO
Project description:Background: The study of human lacrimal gland biology and development is limited. Lacrimal gland tissue is damaged or poorly functional in a number of disease states including dry eye disease. Development of cell based therapies for lacrimal gland diseases requires a better understanding of the gene expression and signaling pathways in lacrimal gland. Differential gene expression analysis between lacrimal gland and other embryologically similar tissues may be helpful in furthering our understanding of lacrimal gland development. Methods: We performed global gene expression analysis of human lacrimal gland tissue using Affymetrix ® gene expression arrays. Primary data from our laboratory was compared with datasets available in the NLM GEO database for other surface ectodermal tissues including salivary gland, skin, conjunctiva and corneal epithelium. Results: The analysis revealed statistically significant difference in the gene expression of lacrimal gland tissue compared to other ectodermal tissues. The lacrimal gland specific, cell surface secretory protein encoding genes and critical signaling pathways which distinguish lacrimal gland from other ectodermal tissues are described. Conclusions: Differential gene expression in human lacrimal gland compared with other ectodermal tissue types revealed interesting patterns which may serve as the basis for future studies in directed differentiation among other areas.
2017-01-03 | GSE89827 | GEO
Project description:Although normal function of the lacrimal gland (LG) is essential for vision (and thus, for human well-being), the LG remains rather poorly understood at molecular level. The purpose of this study was to identify new genes and signaling cascades involved in LG development.
2017-03-01 | GSE78062 | GEO
Project description:In this study, we transferred gut microbiota of SS-like autoimmune dry eye disease model mice to conventional B6 mice (NOD-FMT). After the transfer, NOD-FMT mice experienced a dramatic change in the gut microbiomes and showed clinicopathological features of SS, including increased corneal fluorescein staining score, decreased tear production, elevated levels of IL-6 mRNA, decreased levels of MUC5AC mRNA encoding mucin. Additionally, we observed that NOD-FMT mice shared stereotypic B cell receptor (BCR) clonotypes with a much higher frequency compared to control group. B cell clones encoding these stereotypic BCR clonotypes developed and expanded locally in the lacrimal gland, and achieved systemic presence in certain clonotypes.
2024-06-26 | GSE263577 | GEO