WNT Mimetic-Induced Lacrimal Gland Regeneration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1256503 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR33346422_1.fastq.gz | Fastqsanger.gz | |||
| SRR33346422_2.fastq.gz | Fastqsanger.gz | |||
| SRR33346424_1.fastq.gz | Fastqsanger.gz | |||
| SRR33346424_2.fastq.gz | Fastqsanger.gz |
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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: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: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.
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Project description:To identify the transcriptomic signature of adenoid cystic carcinoma of the lacrimal gland (LGACC), we performed RNA sequencing on LGACC tumor samples and normal lacrimal gland samples.
2023-07-05 | GSE228914 | GEO
Project description:Transcriptional Characterization of healthy lacrimal gland
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Project description:To analyze the gene expression of mouse embryonic lacrimal gland and its developmental related organs such as harderian gland and eye lid. We performed microarray using them.
2017-08-13 | GSE71867 | GEO
Project description:RNA-Seq of embryonic, adult lacrimal gland and lacrimal gland stem cells
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Project description:Tears are essential for the maintenance of the terrestrial animal ocular surface and the lacrimal gland is the source of the aqueous layer of the tear film. Despite the importance of the lacrimal gland in ocular health, molecular aspects of its development remain poorly understood. We have identified a noncoding RNA (miR-205) as an essential gene for lacrimal gland development. Knockout mice lacking miR-205 fail to develop lacrimal glands, establishing this noncoding RNA as a key regulator of lacrimal bud initiation. RNA-seq analysis uncovered several up-regulated miR-205 targets, including Inppl1, a negative regulator of Akt signaling. Data indicate that Akt signaling is required within lacrimal gland epithelia and is activated by Fgf10. Furthermore, combinatorial epistatic deletion of Fgf10 and miR-205 in mice exacerbates the lacrimal gland phenotype. We develop a molecular rheostat model where miR-205 modulates signaling pathways downstream of Fgf10 to regulate glandular development. These data show that a single microRNA is a key regulator for lacrimal gland initiation in mice and highlights the important role of microRNAs during organogenesis.
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Project description:The goal of this study is to find the transcriptional targets downstream of PI3K signaling during lacrimal gland development. We performed laser capture microdissection of the lacrimal gland epithelial tissue at embryonic day E14.5 from control embryos and mutant embryos containing lacrimal gland-specific deletion of PI3K subunits. After tissue harvest, RNA was extracted, conversion to cDNA and amplification was performed by Clontech SMART-seq v4 Ultra low input RNA kit,and cDNA library construction was performed using Nextera XT DNA library preparation kit by core facility at Columbia university prior to RNA sequencing. After preparation of cDNA library, each sample was sequenced using Illumina platform
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