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Teratogen screening using transcriptome profiling of differentiating human embryonic stem cells.

Mayshar Y, Yanuka O, Benvenisty N - J. Cell. Mol. Med. (2010)

Bottom Line: Our results point to the potency of specific teratogens and their affected tissues and pathways.Specifically, we could show that ethanol caused dramatic increase in endodermal differentiation, RA caused misregulation of neural development and thalidomide affected both these processes.We thus propose this method as a valuable addition to currently available animal screening approaches.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.

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Related in: MedlinePlus

Ethanol, RA and thalidomide treatments lead to major global gene expression changes in human EBs. (A) Histogram of the total number of up-regulated (blue) and down-regulated (red) genes induced by each of the treatments in the study. (B) Tissue classification of the affected genes. Shown separately are the up-regulated and down-regulated genes from those treatments showing significant expression changes, classified according to tissue specific genes (as described in ‘Materials and methods’). Significance was calculated relative to the expected number of tissue specific genes using a chi-square independence test and corrected for multiple testing (Bonferroni). (For the complete list of genes see Table S1.)
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fig01: Ethanol, RA and thalidomide treatments lead to major global gene expression changes in human EBs. (A) Histogram of the total number of up-regulated (blue) and down-regulated (red) genes induced by each of the treatments in the study. (B) Tissue classification of the affected genes. Shown separately are the up-regulated and down-regulated genes from those treatments showing significant expression changes, classified according to tissue specific genes (as described in ‘Materials and methods’). Significance was calculated relative to the expected number of tissue specific genes using a chi-square independence test and corrected for multiple testing (Bonferroni). (For the complete list of genes see Table S1.)

Mentions: In this study we treated developing EBs for 7 days with various teratogens at concentrations corresponding to documented human serum levels [8, 22]. Caffeine as a negative control was used at a concentration shown to induce malformations in mice [18]. Following treatment, gene expression was analysed using DNA microarrays. Expression results were analysed relative to their respective untreated controls and genes whose expression was significantly changed (over 2-fold) were counted. Lithium, caffeine and 0.5% ethanol produced little or no effect. Higher doses of ethanol (1.5% and 2%), RA and thalidomide had more dramatic effects with several hundred probesets changing in their levels of expression (Fig. 1A).


Teratogen screening using transcriptome profiling of differentiating human embryonic stem cells.

Mayshar Y, Yanuka O, Benvenisty N - J. Cell. Mol. Med. (2010)

Ethanol, RA and thalidomide treatments lead to major global gene expression changes in human EBs. (A) Histogram of the total number of up-regulated (blue) and down-regulated (red) genes induced by each of the treatments in the study. (B) Tissue classification of the affected genes. Shown separately are the up-regulated and down-regulated genes from those treatments showing significant expression changes, classified according to tissue specific genes (as described in ‘Materials and methods’). Significance was calculated relative to the expected number of tissue specific genes using a chi-square independence test and corrected for multiple testing (Bonferroni). (For the complete list of genes see Table S1.)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4373338&req=5

fig01: Ethanol, RA and thalidomide treatments lead to major global gene expression changes in human EBs. (A) Histogram of the total number of up-regulated (blue) and down-regulated (red) genes induced by each of the treatments in the study. (B) Tissue classification of the affected genes. Shown separately are the up-regulated and down-regulated genes from those treatments showing significant expression changes, classified according to tissue specific genes (as described in ‘Materials and methods’). Significance was calculated relative to the expected number of tissue specific genes using a chi-square independence test and corrected for multiple testing (Bonferroni). (For the complete list of genes see Table S1.)
Mentions: In this study we treated developing EBs for 7 days with various teratogens at concentrations corresponding to documented human serum levels [8, 22]. Caffeine as a negative control was used at a concentration shown to induce malformations in mice [18]. Following treatment, gene expression was analysed using DNA microarrays. Expression results were analysed relative to their respective untreated controls and genes whose expression was significantly changed (over 2-fold) were counted. Lithium, caffeine and 0.5% ethanol produced little or no effect. Higher doses of ethanol (1.5% and 2%), RA and thalidomide had more dramatic effects with several hundred probesets changing in their levels of expression (Fig. 1A).

Bottom Line: Our results point to the potency of specific teratogens and their affected tissues and pathways.Specifically, we could show that ethanol caused dramatic increase in endodermal differentiation, RA caused misregulation of neural development and thalidomide affected both these processes.We thus propose this method as a valuable addition to currently available animal screening approaches.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.

Show MeSH
Related in: MedlinePlus