Dataset Information

Comparative Gene Expression Analysis of Mouse and Human Cardiac Maturation.

ABSTRACT: Understanding how human cardiomyocytes mature is crucial to realizing stem cell-based heart regeneration, modeling adult heart diseases, and facilitating drug discovery. However, it is not feasible to analyze human samples for maturation due to inaccessibility to samples while cardiomyocytes mature during fetal development and childhood, as well as difficulty in avoiding variations among individuals. Using model animals such as mice can be a useful strategy; nonetheless, it is not well-understood whether and to what degree gene expression profiles during maturation are shared between humans and mice. Therefore, we performed a comparative gene expression analysis of mice and human samples. First, we examined two distinct mice microarray platforms for shared gene expression profiles, aiming to increase reliability of the analysis. We identified a set of genes displaying progressive changes during maturation based on principal component analysis. Second, we demonstrated that the genes identified had a differential expression pattern between adult and earlier stages (e.g., fetus) common in mice and humans. Our findings provide a foundation for further genetic studies of cardiomyocyte maturation.

SUBMITTER: Uosaki H

PROVIDER: S-EPMC4996857 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Comparative Gene Expression Analysis of Mouse and Human Cardiac Maturation.

Uosaki Hideki H Taguchi Y-H YH

Genomics, proteomics & bioinformatics 20160716 4

Understanding how human cardiomyocytes mature is crucial to realizing stem cell-based heart regeneration, modeling adult heart diseases, and facilitating drug discovery. However, it is not feasible to analyze human samples for maturation due to inaccessibility to samples while cardiomyocytes mature during fetal development and childhood, as well as difficulty in avoiding variations among individuals. Using model animals such as mice can be a useful strategy; nonetheless, it is not well-understoo ...[more]

PMID: 27431744

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Project description:The application of complex network modeling to analyze large co-expression data sets has gained traction during the last decade. In particular, the use of the weighted gene co-expression network analysis framework has allowed an unbiased and systems-level investigation of genotype-phenotype relationships in a wide range of systems. Since mouse is an important model organism for biomedical research on human disease, it is of great interest to identify similarities and differences in the functional roles of human and mouse orthologous genes. Here, we develop a novel network comparison approach which we demonstrate by comparing two gene-expression data sets from a large number of human and mouse tissues. The method uses weighted topological overlap alongside the recently developed network-decomposition method of s-core analysis, which is suitable for making gene-centrality rankings for weighted networks. The aim is to identify globally central genes separately in the human and mouse networks. By comparing the ranked gene lists, we identify genes that display conserved or diverged centrality-characteristics across the networks. This framework only assumes a single threshold value that is chosen from a statistical analysis, and it may be applied to arbitrary network structures and edge-weight distributions, also outside the context of biology. When conducting the comparative network analysis, both within and across the two species, we find a clear pattern of enrichment of transcription factors, for the homeobox domain in particular, among the globally central genes. We also perform gene-ontology term enrichment analysis and look at disease-related genes for the separate networks as well as the network comparisons. We find that gene ontology terms related to regulation and development are generally enriched across the networks. In particular, the genes FOXE3, RHO, RUNX2, ALX3 and RARA, which are disease genes in either human or mouse, are on the top-10 list of globally central genes in the human and mouse networks.

Project description:BACKGROUND: Pre-implantation development is a crucial step in successful implantation and pregnancy in mammals. It has been studied in depth, but mostly in laboratory animal models. Less is known about the regulatory mechanism involved in the pre-implantation development in humans and about the comparative aspects. METHODS: Here, we employed the microarray datasets from the public database library of GEO and applied comparative analysis of genome wide temporal gene expression data based on statistical analysis and functional annotation for both mouse and human, demonstrating the discordance between the regulatory mechanisms of both mouse and human pre-implantation development. RESULTS: There were differences between mouse and human pre-implantation development both in the global gene expression pattern and in the expression changes of individual genes at each stage, including different major transient waves of transcription profiles and some stage-specific genes and significantly related pathways. There also appeared to be different functional changes from one stage to another between mouse and human. CONCLUSIONS: The analysis presented here lead to interesting and complementary conclusions that the regulatory mechanism of human pre-implantation development is not completely the same as the mouse. Not as the fact that 1-cell to 2-cell stage is important for mouse pre-implantation development, the 4-cell stage and 8-cell stage are both essential for human. Unlike in mouse, of which most of pathways found were related to energy, RNA and protein metabolism, the identified pathways in human were mostly disease-related and associated with human pre-implantation embryonic development. All of these suggest that a further comparative analysis should be required for applying the result of mouse expression data to human research or therapy, particularly in pre-implantation developments. Our study provides several potential targets of genes and pathways for studying the regulatory mechanism of human pre-implantation development using mouse model.

Dataset Information

Comparative Gene Expression Analysis of Mouse and Human Cardiac Maturation.

Publications

Comparative Gene Expression Analysis of Mouse and Human Cardiac Maturation.

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