Analysis of Information Flow for Systematic Understanding of Neuronal Cell Differentiation

초록

For successful differentiation, stem cells are under an efficient control of the flow of information that enables them to possess the necessary phenotypic properties. In a cellular system, the external and internal environmental factors have a significant influence on the change of the quantity and route of information. This study is aimed at predicting the flow of information that systematically regulates the gene expression in a cellular system, using time-series microarray data obtained from hES cell-derived neural precursors. We sought the genes activated at the forefront of environmental changes and the properties of information induced by various environmental factors. For this purpose, we defined the relative entropy and coherent information of gene expression as the measures of the relatedness between genes. Furthermore, we identified some blocks of the measure of coherent information, each of which represents a group of genes that would share the common information about neuronal differentiation. The biological significance of the major flow of information between the coherent information blocks was inferred with regard to the expression of physiological and phenotypic properties related to neuronal differentiation. The major route of information flow and the coherent information blocks showed that the cellular system was mainly influenced by at least two kinds of environmental factors through some genes as the sources of information in their blocks: the removal of bFGF from the cell-culture media for the induction of neuronal differentiation (NHLH1, ALDH1A2, TNMD, SALL3, etc) and the regular replacement of the cell-culture media (LEFTY2, ADM, MT1G, HMX1, etc). These genes are believed to play an important role in determining the biological property of the blocks as the starting point of information. The biological significance of the block including LEFTY2, a member of TGFβ superfamily, is expected to the induction of the neuronal differentiation regulated by the TGFβ-signaling. In addition, we expect that the blocks, including NHLH1, HMX1 and SALL3, would have the biological significance in the formation of the nervous system.