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MiR-205 is a critical regulator of lacrimal gland development

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE95108 | GEO | 2017/04/01

SECONDARY ACCESSION(S): PRJNA376111

REPOSITORIES: GEO

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Mus musculus

Project description:miR-205 is a critical regulator of lacrimal gland development

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Project description:The goal of the study is to find the transcriptional targets downstream of Shp2-mediated signaling regulating Fgf10 production in the lacrimal gland mesenchyme. In order to look for the potential targets, we performed laser capture microdissection of the lacrimal gland mesenchyme tissue at embryonic day E14.5 from control embryos as well as mutant embryos containing neural crest-specific deletion of Shp2. After tissue harvest, RNA was extracted and conversion to cDNA as well as amplification was performed by NUGEN’s ovation kit v2. After preparation of cDNA library, each sample was sequenced using Illumina platform.

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A basal specific microRNA promotes tumorigenesis in both basal and luminal cells of murine prostate gland

Project description:Recent studies demonstrate both basal and luminal cells of the prostate gland can initiate tumorigenesis upon oncogenic transformation. However, it remains unclear how molecular mechanisms operating within each cell lineage contribute to the initiation and progression of the prostate cancer. Here we investigate functions of individual miRNAs using genetically engineered mouse models. By both quantitative miR-Seq and in situ hybridization, we identify microRNA-205 (miR-205) as the most highly expressed miRNA and specific to the basal cells in the prostate. MicroRNA-205 expression is further elevated in the basal cells in the well-established Pten null tumorigenic mouse model. To investigate the role of miR-205 in Pten-deletion mediated tumorigenesis, we generated a Pten/miR-205 double knockout mouse model. Concurrent deletion of both miR-205 and Pten significantly compromised tumor progression in both basal and luminal compartments. We observed significantly reduced tumor size and compromised proliferation in both basal and luminal cells. We have previously demonstrated a critical requirement of miR-205 for maintaining the PI(3)K signaling and pAkt levels in skin stem cells. Consistent with this role, we observed strong reduction of pAkt and significantly increased cellular senescence in the basal cells of the dKO, compared to the Pten KO alone. These results suggest that miR-205 is cell-autonomously required for the tumorigenesis of the basal cells. Taken together, we have identified miR-205 as an important regulator in prostate cancer. Our study also reveals an essential and unexpected role of the basal cells for promoting prostate tumorigenesis.

2019-09-16 | GSE75321 | GEO

Characterization of immortalized human lacrimal gland epithelial cells in 2D and 3D cell culture models

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.

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Desiccating stress triggers conjunctival monocyte to macrophage cascade - Implications for Sjögren Syndrome keratoconjunctivitis Desiccation induced monocyte cascade

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Human Lacrimal Gland Gene Expression

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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miR-205-5p Inhibits Human Endometriosis Progression by Targeting ANGTP2 in Endometrial Stromal Cells

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Bulk RNA-seq of trigeminal ganglia from C57BL/6 (wild-type) and Rag1KO mice with dry eye (extraorbital lacrimal gland excision model) versus sham-operated controls

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2024-04-01 | E-MTAB-13945 | biostudies-arrayexpress

microRNA expression during ovine adult mammary gland development

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