Dataset Information

An organogenesis network-based comparative transcriptome analysis for understanding early human development in vivo and in vitro.

ABSTRACT:

Background

Integrated networks hold great promise in a variety of contexts. In a recent study, we have combined expression and interaction data to identify a putative network underlying early human organogenesis that contains two modules, the stemness-relevant module (hStemModule) and the differentiation-relevant module (hDiffModule). However, owing to its hypothetical nature, it remains unclear whether this network allows for comparative transcriptome analysis to advance our understanding of early human development, both in vivo and in vitro.

Results

Based on this integrated network, we here report comparisons with the context-dependent transcriptome data from a variety of sources. By viewing the network and its two modules as gene sets and conducting gene set enrichment analysis, we demonstrate the network's utility as a quantitative monitor of the stem potential versus the differentiation potential. During early human organogenesis, the hStemModule reflects the generality of a gradual loss of the stem potential. The hDiffModule indicates the stage-specific differentiation potential and is therefore not suitable for depicting an extended developmental window. Processing of cultured cells of different types further revealed that the hStemModule is a general indicator that distinguishes different cell types in terms of their stem potential. In contrast, the hDiffModule cannot distinguish between differentiated cells of different types but is able to predict differences in the differentiation potential of pluripotent cells of different origins. We also observed a significant positive correlation between each of these two modules and early embryoid bodies (EBs), which are used as in vitro differentiation models. Despite this, the network-oriented comparisons showed considerable differences between the developing embryos and the EBs that were cultured in vitro over time to try to mimic in vivo processes.

Conclusions

We strongly recommend the use of these two modules either when pluripotent cell types of different origins are involved or when the comparisons made are constrained to the in vivo embryos during early human organogenesis (and an equivalent in vitro differentiation models). Network-based comparative transcriptome analysis will contribute to an increase in knowledge about human embryogenesis, particularly when only transcriptome data are currently available. These advances will add an extra dimension to network applications.

SUBMITTER: Fang H

PROVIDER: S-EPMC3141417 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Publications

An organogenesis network-based comparative transcriptome analysis for understanding early human development in vivo and in vitro.

Fang Hai H Jin Wen W Yang Ying Y Jin Ying Y Zhang Ji J Wang Kankan K

BMC systems biology 20110706

<h4>Background</h4>Integrated networks hold great promise in a variety of contexts. In a recent study, we have combined expression and interaction data to identify a putative network underlying early human organogenesis that contains two modules, the stemness-relevant module (hStemModule) and the differentiation-relevant module (hDiffModule). However, owing to its hypothetical nature, it remains unclear whether this network allows for comparative transcriptome analysis to advance our understandi ...[more]

PMID: 21733158

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Project description:We here report transcriptome profiling of human embryos at six successive developmental stages (i.e., Carnegie Stages 9 to 14), representing the first comprehensive gene expression database of early human organogenesis. Through a series of data mining and comparisons with the transcriptome during mouse embryogenesis and the disparate genomic data in human embryonic stem cells, we revealed that development potential during early human organogenesis is orchestrated by two dominant categories of genes. Specifically, most gradually induced genes are largely differentiation related whereas those gradually repressed are involved in both stemness- and differentiation-relevant aspects of the developmental potential. Further through integrative mining we uncovered a molecular network that well characterizes stemness- and differentiation-relevant aspects of developmental potentials during early human organogenesis. Analysis of published data showed that the network could serve to evaluate various differentiation models. Our results make a significant step towards understanding of human embryogenesis at a molecular level and suggest that developmental potentials are under control of shared regulatory events. With the consent of subjects and of the Ethical Review Board of the Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine,we collected human post-implantation embryos at six successive time periods: Carnegie Stages 9 to 14 (E20 to E32), covering the first third of organogenesis. Using the Affymetrix HG-U133A Genechip microarrays, three replicates were independently profiled for each stage to minimize the influence of the embryo-to-embryo variation. Raw expression data were normalized using Robust Multi-array Averaging (RMA) with quantile normalization. The resultant expression data were imported into Extraction of Differential Gene Expression (EDGE) software for the detection of probesets exhibiting the consistent changes within the triplicates and differential expression (denoted as hORG expression matrix). The hORG expression matrix was subjected to Linear Models for Microarray Data (LIMMA) bioconductor library for identification of stage-transitive transcriptome changes, and self-organizing map combined with singular value decomposition (SOM-SVD) as well as SOM-based two-phase gene clustering for the topology-preserving extraction of temporal expression patterns. Hypergeometric distribution-based enrichment analyses were performed to explore the underlying biological relevance of gene groups of interest using diverse external annotated databases. The Cytoscape plug-in jActiveModules was modified to identify expression-active connected subnetworks in the compiled human interaction/association network.

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Dataset Information

An organogenesis network-based comparative transcriptome analysis for understanding early human development in vivo and in vitro.

Background

Results

Conclusions

Publications

An organogenesis network-based comparative transcriptome analysis for understanding early human development in vivo and in vitro.

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