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Microarray analysis of sexually dimorphic gene expression in human minor salivary glands.

ABSTRACT: OBJECTIVE:We hypothesized that differential mRNA transcription between the sexes may be linked to the 9:1 female-to-male gender-related relative risk for the development of Sjögren's syndrome (SS), an autoimmune disease that leads to inflammation and dysfunction in the lachrymal and salivary glands. SUBJECTS AND METHODS:RNA from minor salivary glands was collected from nine healthy volunteers (four men and five women) and analyzed using the Agilent 4 × 44K human microarray platform. Differential expression was confirmed by qRT-PCR. RESULTS:Comparison of the transcriptome of minor salivary glands from normal male and female volunteers with that of salivary glands and secretory epithelia identified a number of gender, species, and tissue-specific gene expression patterns. These differences include, but are not limited to, a diverse set of genes involved in immune modulation, chemotactic control, inhibition of complement, metabolism, and neurogenesis. CONCLUSION:Analysis of these changes provides insight into the protective and predisposing molecular factors that may be involved in the development of Sjögren's syndrome. Some of the gene changes observed in this study correlate with previously observed sexual dimorphisms in salivary gland function and also illustrate several new targets for further investigation.

SUBMITTER: Michael D

PROVIDER: S-EPMC4083356 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Microarray analysis of sexually dimorphic gene expression in human minor salivary glands.

Michael D D Soi S S Cabera-Perez J J Weller M M Alexander S S Alevizos I I Illei Gg G Chiorini Ja J

Oral diseases 20110808 7

<h4>Objective</h4>We hypothesized that differential mRNA transcription between the sexes may be linked to the 9:1 female-to-male gender-related relative risk for the development of Sjögren's syndrome (SS), an autoimmune disease that leads to inflammation and dysfunction in the lachrymal and salivary glands.<h4>Subjects and methods</h4>RNA from minor salivary glands was collected from nine healthy volunteers (four men and five women) and analyzed using the Agilent 4 × 44K human microarray platfor ...[more]

PMID: 21819492

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Project description:BackgroundFetal sex and placental development impact pregnancy outcomes and fetal-maternal health, but the critical timepoint of placenta establishment in first trimester is understudied in human pregnancies.MethodsPregnant subjects were recruited in late first trimester (weeks 10-14) at time of chorionic villus sampling, a prenatal diagnostic test. Leftover placenta tissue was collected and stored until birth outcomes were known, then DNA and RNA were isolated from singleton, normal karyotype pregnancies resulting in live births. DNA methylation was measured with the Illumina Infinium MethylationEPIC BeadChip array (n = 56). Differential methylation analysis compared 25 females versus 31 males using a generalized linear model on 743,461 autosomal probes. Gene expression sex differences were analyzed with RNA-sequencing (n = 74). An integrated analysis was performed using linear regression to correlate gene expression and DNA methylation in 51 overlapping placentas.ResultsMethylation analysis identified 151 differentially methylated probes (DMPs) significant at false discovery rate < 0.05, including 89 (59%) hypermethylated in females. Probe cg17612569 (GABPA, ATP5J) was the most significant CpG site, hypermethylated in males. There were 11 differentially methylated regions affected by fetal sex, with transcription factors ZNF300 and ZNF311 most significantly hypermethylated in males and females, respectively. RNA-sequencing identified 152 genes significantly sexually dimorphic at false discovery rate < 0.05. The 151 DMPs were associated with 18 genes with gene downregulation (P < 0.05) in the direction of hypermethylation, including 2 genes significant at false discovery rate < 0.05 (ZNF300 and CUB and Sushi multiple domains 1, CSMD1). Both genes, as well as Family With Sequence Similarity 228 Member A (FAM228A), showed significant correlation between DNA methylation and sexually dimorphic gene expression, though FAM228A DNA methylation was less sexually dimorphic. Comparison with other sex differences studies found that cg17612569 is male-hypermethylated across gestation in placenta and in human blood up to adulthood.ConclusionsOverall, sex dimorphic differential methylation with associated differential gene expression in the first trimester placenta is small, but there remain significant genes that may be regulated through methylation leading to differences in the first trimester placenta.

Project description:BackgroundXerostomia is a salivary gland dysfunction that negatively impacts the life quality of patients; however, there is no effective treatment for xerostomia. Bioengineered organs, generated using stem cells obtained from newborn salivary glands and ligated injury models, are a new organ transplantation strategy that could be feasible for xerostomia treatment. Reconstruction of salivary gland organoids by seed cells obtained from human minor salivary glands will offer theoretical fundaments and technology support for clinical application and organ regeneration research. Herein, we aimed to propose a new method for culturing and enriching adult human minor salivary gland stem cells in vitro in a three-dimensional (3D) environment via Wnt signaling activation.MethodsObtained and characterized human minor salivary gland stem cells (hMSGSCs) with self-organization ability were 3D-cultured to generate organoids. We examined hMSGSCs proliferation and colony formation using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. Telomerase reverse transcriptase staining, flow cytometry, immunofluorescence assay, RNA isolation, RT-PCR, and qPCR were performed to assess hMSGSCs structure and the function of reconstructive organoids in vitro.ResultshMSGSCs showed typical epithelial-like characteristics, such as positive for CD49f and cell KRT expression. hMSGSCs served as adult stem cells in salivary glands and could differentiate into acinar and duct cells. Upon the addition of Noggin, CHIR99021, and Wnt3A to the 3D culture system, hMSGSCs showed higher LGR5 expression and decreased AMY1B and MUC5B expression. Therefore, the Wnt and bone morphogenetic protein (BMP) pathways are important in regulating hMSGSCs self-organization and differentiation.ConclusionsWe showed that the stem cell properties of hMSGSCs in a 3D culture system can be maintained by activating the Wnt signaling pathway and inhibiting the BMP signaling pathway. Our findings contribute new insights on salivary gland organoid generation in vitro.

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Microarray analysis of sexually dimorphic gene expression in human minor salivary glands.

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Microarray analysis of sexually dimorphic gene expression in human minor salivary glands.

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