Differential gene expression in anatomical compartments of the human eye

BACKGROUND: The human eye is composed of multiple compartments, diverse in form, function, and embryologic origin, that work in concert to provide us with our sense of sight. We set out to systematically characterize the global gene expression patterns that specify the distinctive characteristics of the various eye compartments. RESULTS: We used DNA microarrays representing approximately 30,000 human genes to analyze gene expression in the cornea, lens, iris, ciliary body, retina, and optic nerve. The distinctive patterns of expression in each compartment could be interpreted in relation to the physiology and cellular composition of each tissue. Notably, the sets of genes selectively expressed in the retina and in the lens were particularly large and diverse. Genes with roles in immune defense, particularly complement components, were expressed at especially high levels in the anterior segment tissues. We also found consistent differences between the gene expression patterns of the macula and peripheral retina, paralleling the differences in cell layer densities between these regions. Based on the hypothesis that genes responsible for diseases that affect a particular eye compartment are likely to be selectively expressed in that compartment, we compared our gene expression signatures with genetic mapping studies to identify candidate genes for diseases affecting the cornea, lens, and retina. CONCLUSION: Through genome-scale gene expression profiling, we were able to discover distinct gene expression 'signatures' for each eye compartment and identified candidate disease genes that can serve as a reference database for investigating the physiology and pathophysiology of the eye

Phenotypic responses to mechanical stress in fibroblasts from tendon, cornea and skin

Primary fibroblasts isolated from foetal mouse cornea, skin and tendon were subjected to linear shear stress and analysed for morphological parameters and by microarray, as compared with unstimulated controls. Approx. 350 genes were either up- or down-regulated by a significant amount, with 51 of these being common to all three cell types. Approx. 50% of altered genes in tendon and cornea fibroblasts were changed in common with one of the other cell types, with the remaining approx. 50% being specific to tendon or cornea. In skin fibroblasts, however, less than 25% of genes whose transcription was altered were specific only to skin. The functional spectrum of genes that were up- or down-regulated was diverse, with apparent house-keeping genes forming the major category of up-regulated genes. However, a significant number of genes associated with cell adhesion, extracellular matrix and matrix remodelling, as well as cytokines and other signalling factors, were also affected. Somewhat surprisingly, in these latter categories the trend was towards a reduction in mRNA levels. Verification of the mRNA quantity of a subset of these genes was performed by reverse transcriptase PCR and was found to be in agreement with the microarray analysis. These findings provide the first in-depth analysis of phenotypic differences between fibroblast cells from different tissue sources and reveal the responses of these cells to mechanical stress

microRNAs and EMT in mammary cells and breast cancer

MicroRNAs are master regulators of gene expression in many biological and pathological processes, including mammary gland development and breast cancer. The differentiation program termed the epithelial to mesenchymal transition (EMT) involves changes in a number of microRNAs. Some of these microRNAs have been shown to control cellular plasticity through the suppression of EMT-inducers or to influence cellular phenotype through the suppression of genes involved in defining the epithelial and mesenchymal cell states. This has led to the suggestion that microRNAs maybe a novel therapeutic target for the treatment of breast cancer. In this review, we will discuss microRNAs that are involved in EMT in mammary cells and breast cancer.Josephine A. Wright, Jennifer K. Richer and Gregory J. Goodal