A Time Course Microarray Study of Gene Expression in the Mouse Lacrimal Gland after Acute Corneal Trauma

Fang, Yuan; Choi, Dongseok; Searles, Robert P.; Mathers, William D.

doi:10.1167/iovs.04-0677

Cited by 17 publications

(7 citation statements)

References 59 publications

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“…For example, a corneal wound induces alteration of the gene expression profile of the lacrimal gland. 7 Similarly, dysfunctions of or injury to one or more components of the Ocular Surface System can lead to systemwide sequelae such as cicatrizing diseases and dry eye-the latter being defined as a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability, with potential damage to the ocular surface. 8 For example, meibomian or lacrimal gland disease induces dry eye.…”

Section: The Ocular Surface Systemmentioning

confidence: 99%

The Ocular Surface: The Challenge to Enable and Protect Vision

Gipson

2007

Invest. Ophthalmol. Vis. Sci.

271

209

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Section: The Ocular Surface Systemmentioning

confidence: 99%

The Ocular Surface: The Challenge to Enable and Protect Vision

Gipson

2007

Invest. Ophthalmol. Vis. Sci.

271

209

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“…Differential gene expression analysis of RNA-Seq and microarray data has become a common tool to compare gene expression between individuals, tissues, and cell subsets. A few studies used microarrays to investigate gene expression in the lacrimal gland following acute corneal trauma, loss of parasympathetic secretion and botulinum toxin B injury [15–17]. RNA-seq has not been used yet to investigate gene expression changes occurring during lacrimal gland tissue repair following an inflammatory injury process.…”

Section: Introductionmentioning

confidence: 99%

RNA-Seq and CyTOF immuno-profiling of regenerating lacrimal glands identifies a novel subset of cells expressing muscle-related proteins

et al. 2017

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The purpose of the present studies was to use CyTOF and RNA-Seq technologies to identify cells and genes involved in lacrimal gland repair that could be targeted to treat diseases of lacrimal gland dysfunction. Lacrimal glands of female BALB/c mice were experimentally injured by intra-glandular injection of interleukin 1 alpha (IL-1α). The lacrimal glands were harvested at various time points following injury (1 to 14 days) and used to either prepare single cell suspensions for CyTOF immuno-phenotyping analyses or to extract RNA for gene expression studies using RNA-Seq. CyTOF immuno-phenotyping identified monocytes and neutrophils as the major infiltrating populations 1 and 2 days post injury. Clustering of significantly differentially expressed genes identified 13 distinct molecular signatures: 3 associated with immune/inflammatory processes included genes up-regulated at days 1–2 and 3 associated with reparative processes with genes up-regulated primarily between days 4 and 5. Finally, clustering identified 65 genes which were specifically up-regulated 2 days post injury which was enriched for muscle specific genes. The expression of select muscle-related proteins was confirmed by immunohistochemistry which identified a subset of cells expressing these proteins. Double staining experiments showed that these cells are distinct from the myoepithelial cells. We conclude that experimentally induced injury to the lacrimal gland leads to massive infiltration by neutrophils and monocytes which resolved after 3 days. RNAseq and immunohistochemistry identified a group of cells, other than myoepithelial cells, that express muscle-related proteins that could play an important role in lacrimal gland repair.

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“…We further identified the pre-disease state through I -score in three real time-course datasets, i.e., the gene expression profiling dataset (GSE2565) generated from a mouse experiment, in which pulmonary edema was triggered by inhalation of carbonyl chloride [ 30 ]; the microarray dataset (GSE1393) of acute corneal trauma after a chemical burn with silver nitrate was also obtained from a mouse experiment, which is carried out for examining the effect of stimulation stress produced by chemical burn, in comparison with the non-stimulated control animals [ 31 ]; and the genomic dataset (GSE13009) derived from an study on human breast cancer cells, in which heregulin induced sustained signal activity in MCF-7 cells and triggered an irreversible cell phenotype change to differentiation [ 32 ]. The application on the lung injury dataset is set as a concrete demonstration.…”

Section: Resultsmentioning

confidence: 99%

Detecting the tipping points in a three-state model of complex diseases by temporal differential networks

Chen

Liu

et al. 2017

J Transl Med

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BackgroundThe progression of complex diseases, such as diabetes and cancer, is generally a nonlinear process with three stages, i.e., normal state, pre-disease state, and disease state, where the pre-disease state is a critical state or tipping point immediately preceding the disease state. Traditional biomarkers aim to identify a disease state by exploiting the information of differential expressions for the observed molecules, but may fail to detect a pre-disease state because there are generally little significant differences between the normal and pre-disease states. Thus, it is challenging to signal the pre-disease state, which actually implies the disease prediction.MethodsIn this work, by exploiting the information of differential associations among the observed molecules between the normal and pre-disease states, we propose a temporal differential network based computational method to accurately signal the pre-disease state or predict the occurrence of severe disease. The theoretical foundation of this work is the quantification of the critical state using dynamical network biomarkers.ResultsConsidering that there is one stationary Markov process before reaching the tipping point, a novel index, inconsistency score (I-score), is proposed to quantitatively measure the change of the stationary processes from the normal state so as to detect the onset of pre-disease state. In other words, a drastic increase of I-score implies the high inconsistency with the preceding stable state and thus signals the upcoming critical transition. This approach is applied to the simulated and real datasets of three diseases, which demonstrates the effectiveness of our method for predicting the deterioration into disease states. Both functional analysis and pathway enrichment also validate the computational results from the perspectives of both molecules and networks.ConclusionsAt the molecular network level, this method provides a computational way of unravelling the underlying mechanism of the dynamical progression when a biological system is near the tipping point, and thus detecting the early-warning signal of the imminent critical transition, which may help to achieve timely intervention. Moreover, the rewiring of differential networks effectively extracts discriminatively interpretable features, and systematically demonstrates the dynamical change of a biological system.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1320-7) contains supplementary material, which is available to authorized users.

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A Time Course Microarray Study of Gene Expression in the Mouse Lacrimal Gland after Acute Corneal Trauma

Abstract: This study demonstrates that corneal trauma has profound effects on the regulation of gene expression in the lacrimal gland and may provide genetic evidence for a cornea-to-lacrimal gland feedback mechanism in dry eye.

Cited by 17 publications

References 59 publications

The Ocular Surface: The Challenge to Enable and Protect Vision

The Ocular Surface: The Challenge to Enable and Protect Vision

RNA-Seq and CyTOF immuno-profiling of regenerating lacrimal glands identifies a novel subset of cells expressing muscle-related proteins

Detecting the tipping points in a three-state model of complex diseases by temporal differential networks

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