Identification of stage-specific gene expression signatures in response to retinoic acid during the neural differentiation of mouse embryonic stem cells
AbstractWe have previously established a protocol for the neural differentiation of mouse embryonic stem cells (mESCs) as an efficient tool to evaluate the neurodevelopmental toxicity of environmental chemicals. Here, we described a multivariate bioinformatic approach to identify the stage-specific...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fgene.2012.00141/full |
| _version_ | 1828158366370758656 |
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| author | Hiromi eAkanuma Xian-Yang eQin Xian-Yang eQin Reiko eNagano Tin-Tin eWin-Shwe Satoshi eImanishi Hiroko eZaha Tomokazu eFukuda Jun eYoshinaga Seiichiroh eOhsako Hideko eSone |
| author_facet | Hiromi eAkanuma Xian-Yang eQin Xian-Yang eQin Reiko eNagano Tin-Tin eWin-Shwe Satoshi eImanishi Hiroko eZaha Tomokazu eFukuda Jun eYoshinaga Seiichiroh eOhsako Hideko eSone |
| author_sort | Hiromi eAkanuma |
| collection | DOAJ |
| description | AbstractWe have previously established a protocol for the neural differentiation of mouse embryonic stem cells (mESCs) as an efficient tool to evaluate the neurodevelopmental toxicity of environmental chemicals. Here, we described a multivariate bioinformatic approach to identify the stage-specific gene sets associated with neural differentiation of mESCs. We exposed mESCs (B6G-2 cells) to 10-8 M or 10-7 M of retinoic acid (RA) for 4 days during embryoid body formation and then performed morphological analysis on day of differentiation (DoD) 8 and 36, or genomic microarray analysis on DoD 0, 2, 8 and 36. Three gene sets, namely a literature-based gene set (set 1), an analysis-based gene set (set 2) using self-organizing map and principal component analysis, and an enrichment gene set (set 3), were selected by the combined use of knowledge from literatures and gene information selected from the microarray data. A gene network analysis for each gene set was then performed using Bayesian statistics to identify stage-specific gene expression signatures in response to RA during mESC neural differentiation. Our results showed that RA significantly increased the size of neurosphere, neuronal cells and glial cells on DoD 36. In addition, the gene network analysis showed that Gfap, a neural marker, remarkably up-regulates the other genes in gene set 1 and 3, and Gbx2, a neural development marker, significantly up-regulates the other genes in gene set 2 on DoD 36 in the presence of RA. These findings suggest that our protocol for identification of developmental stage specific gene expression and interaction is a useful method for the screening of environmental chemical toxicity during neurodevelopmental periods. |
| first_indexed | 2024-04-11T23:43:51Z |
| format | Article |
| id | doaj.art-dbb7d0a030fc4995b96a4014e7507866 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T23:43:51Z |
| publishDate | 2012-08-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-dbb7d0a030fc4995b96a4014e75078662022-12-22T03:56:44ZengFrontiers Media S.A.Frontiers in Genetics1664-80212012-08-01310.3389/fgene.2012.0014126208Identification of stage-specific gene expression signatures in response to retinoic acid during the neural differentiation of mouse embryonic stem cellsHiromi eAkanuma0Xian-Yang eQin1Xian-Yang eQin2Reiko eNagano3Tin-Tin eWin-Shwe4Satoshi eImanishi5Hiroko eZaha6Tomokazu eFukuda7Jun eYoshinaga8Seiichiroh eOhsako9Hideko eSone10National Institute for Environmental StudiesNational Institute for Environmental StudiesThe University of TokyoNational Institute for Environmental StudiesNational Institute for Environmental StudiesNational Institute for Environmental StudiesNational Institute for Environmental StudiesTohoku UniversityThe University of TokyoGraduate School of Medicine, The University of TokyoNational Institute for Environmental StudiesAbstractWe have previously established a protocol for the neural differentiation of mouse embryonic stem cells (mESCs) as an efficient tool to evaluate the neurodevelopmental toxicity of environmental chemicals. Here, we described a multivariate bioinformatic approach to identify the stage-specific gene sets associated with neural differentiation of mESCs. We exposed mESCs (B6G-2 cells) to 10-8 M or 10-7 M of retinoic acid (RA) for 4 days during embryoid body formation and then performed morphological analysis on day of differentiation (DoD) 8 and 36, or genomic microarray analysis on DoD 0, 2, 8 and 36. Three gene sets, namely a literature-based gene set (set 1), an analysis-based gene set (set 2) using self-organizing map and principal component analysis, and an enrichment gene set (set 3), were selected by the combined use of knowledge from literatures and gene information selected from the microarray data. A gene network analysis for each gene set was then performed using Bayesian statistics to identify stage-specific gene expression signatures in response to RA during mESC neural differentiation. Our results showed that RA significantly increased the size of neurosphere, neuronal cells and glial cells on DoD 36. In addition, the gene network analysis showed that Gfap, a neural marker, remarkably up-regulates the other genes in gene set 1 and 3, and Gbx2, a neural development marker, significantly up-regulates the other genes in gene set 2 on DoD 36 in the presence of RA. These findings suggest that our protocol for identification of developmental stage specific gene expression and interaction is a useful method for the screening of environmental chemical toxicity during neurodevelopmental periods.http://journal.frontiersin.org/Journal/10.3389/fgene.2012.00141/fullPrincipal Component AnalysisBayesian networkneural differentiationRetinoic acidmouse embryonic stem cellsself-organizing map |
| spellingShingle | Hiromi eAkanuma Xian-Yang eQin Xian-Yang eQin Reiko eNagano Tin-Tin eWin-Shwe Satoshi eImanishi Hiroko eZaha Tomokazu eFukuda Jun eYoshinaga Seiichiroh eOhsako Hideko eSone Identification of stage-specific gene expression signatures in response to retinoic acid during the neural differentiation of mouse embryonic stem cells Frontiers in Genetics Principal Component Analysis Bayesian network neural differentiation Retinoic acid mouse embryonic stem cells self-organizing map |
| title | Identification of stage-specific gene expression signatures in response to retinoic acid during the neural differentiation of mouse embryonic stem cells |
| title_full | Identification of stage-specific gene expression signatures in response to retinoic acid during the neural differentiation of mouse embryonic stem cells |
| title_fullStr | Identification of stage-specific gene expression signatures in response to retinoic acid during the neural differentiation of mouse embryonic stem cells |
| title_full_unstemmed | Identification of stage-specific gene expression signatures in response to retinoic acid during the neural differentiation of mouse embryonic stem cells |
| title_short | Identification of stage-specific gene expression signatures in response to retinoic acid during the neural differentiation of mouse embryonic stem cells |
| title_sort | identification of stage specific gene expression signatures in response to retinoic acid during the neural differentiation of mouse embryonic stem cells |
| topic | Principal Component Analysis Bayesian network neural differentiation Retinoic acid mouse embryonic stem cells self-organizing map |
| url | http://journal.frontiersin.org/Journal/10.3389/fgene.2012.00141/full |
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