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(to be completed)

 


ThinkMind // International Journal On Advances in Life Sciences, volume 5, numbers 1 and 2, 2013 // View article lifsci_v5_n12_2013_9


Inference of Gene Regulatory Networks to Detect Toxicity-Specific Effects in Human Embryonic Stem Cells

Authors:
Sachiyo Aburatani
Wataru Fujibuchi
Junko Yamane
Satoshi Imanishi
Reiko Nagano
Hideko Sone
Seiichiroh Ohsako

Keywords: Structural Equation Modeling; Gene Regulatory Network; Embryonic Stem Cell; Environmental Chemicals

Abstract:
Environmental chemicals are known to cause serious developmental problems in embryos. To prevent injurious chemical effects, knowledge of the chemical toxicity mechanisms in human embryos is important. To reveal the functional mechanisms in living cells, inferring a gene regulatory network is a useful approach. We applied our developed statistical methods based on Structural Equation Modeling to infer the gene regulatory networks in human embryonic stem cells. In this study, we improved the SEM approach and applied this enhanced version to expression profiles in human embryonic stem cells exposed to various chemicals. For almost all of the tested chemicals, the cell differentiation-related genes and the neuron development-related genes were intermixed in the inferred networks. Since the chemicals' networks displayed diffusion type shapes, the effects of chemical toxicity are considered to affect a few target genes at first, and then ultimately many genes via regulatory mechanisms. Furthermore, the genes that were finally affected were conserved among chemicals with the same toxicity: Tuj1 in Neurotoxic chemicals, Oct3/4 and Pax6 in Genotoxic chemicals, and Oct3/4 in Carcinogenic chemicals. These finally affected genes are considered to be the results of toxicity-specific effects in ES cells, and they reflected the features of the toxicity. We also found that some chemicals shared the same regulatory mechanism. The detected toxicity-specific effects are valuable for developing methods to prevent chemicals from disturbing normal development.

Pages: 103 to 114

Copyright: Copyright (c) to authors, 2013. Used with permission.

Publication date: June 30, 2013

Published in: journal

ISSN: 1942-2660

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