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Differences in the Early Development of Human and Mouse Embryonic Stem Cells.

Gabdoulline R, Kaisers W, Gaspar A, Meganathan K, Doss MX, Jagtap S, Hescheler J, Sachinidis A, Schwender H - PLoS ONE (2015)

Bottom Line: Many development features were found to be conserved, and a majority of differentially regulated genes have similar expression change in both organisms.However, we also found that some biological processes develop differently; this can clearly be shown, for example, for neuron and sensory organ development.We also detected a larger number of upregulated genes during development of mESCs as compared to hESCs.

View Article: PubMed Central - PubMed

Affiliation: Center for Bioinformatics and Biostatistics, Biological Medical Research Center, Heinrich Heine University, Universitätsstrasse 1, 40225 Düsseldorf, Germany.

ABSTRACT
We performed a systematic analysis of gene expression features in early (10-21 days) development of human vs mouse embryonic cells (hESCs vs mESCs). Many development features were found to be conserved, and a majority of differentially regulated genes have similar expression change in both organisms. The similarity is especially evident, when gene expression profiles are clustered together and properties of clustered groups of genes are compared. First 10 days of mESC development match the features of hESC development within 21 days, in accordance with the differences in population doubling time in human and mouse ESCs. At the same time, several important differences are seen. There is a clear difference in initial expression change of transcription factors and stimulus responsive genes, which may be caused by the difference in experimental procedures. However, we also found that some biological processes develop differently; this can clearly be shown, for example, for neuron and sensory organ development. Some groups of genes show peaks of the expression levels during the development and these peaks cannot be claimed to happen at the same time points in the two organisms, as well as for the same groups of (orthologous) genes. We also detected a larger number of upregulated genes during development of mESCs as compared to hESCs. The differences were quantified by comparing promoters of related genes. Most of gene groups behave similarly and have similar transcription factor (TF) binding sites on their promoters. A few groups of genes have similar promoters, but are expressed differently in two species. Interestingly, there are groups of genes expressed similarly, although they have different promoters, which can be shown by comparing their TF binding sites. Namely, a large group of similarly expressed cell cycle-related genes is found to have discrepant TF binding properties in mouse vs human.

No MeSH data available.


Related in: MedlinePlus

Histogram of p-values (-log2 scale) calculated for TFBSs of clustered gene groups vs random groups of genes of the same size.TFBS overrepresentation p-values for clustered gene groups are shown as impulses, for random groups—as lines. According to this comparison, TFBSs assigned to the group with overrepresentation p-value less than 10−9 (log2P<-29.9) can be considered to be less likely to appear by a chance.
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pone.0140803.g005: Histogram of p-values (-log2 scale) calculated for TFBSs of clustered gene groups vs random groups of genes of the same size.TFBS overrepresentation p-values for clustered gene groups are shown as impulses, for random groups—as lines. According to this comparison, TFBSs assigned to the group with overrepresentation p-value less than 10−9 (log2P<-29.9) can be considered to be less likely to appear by a chance.

Mentions: Groups of genes derived by clustering are assigned TFBSs, whose presence on the promoters has low p-values. In addition to calculating these p-values, indicating significance of single TFBSs for regulation of these gene groups, we performed a separate test to check if our clustered gene groups show TFBS enrichment better than random groups of genes of the same size. These checks are necessary because of the multiple testing nature of TFBS assignments, when even randomly chosen groups can have certain TFBSs assigned a low p-value. The results are shown in Fig 5. Indeed, our groups have assigned TFBSs with far smaller p-values than the random groups, i.e. within this approach we cannot only examine general similarity of the promoters in terms of TFBSs, but also assign TFBSs, which may be relevant to the regulation of particular groups.


Differences in the Early Development of Human and Mouse Embryonic Stem Cells.

Gabdoulline R, Kaisers W, Gaspar A, Meganathan K, Doss MX, Jagtap S, Hescheler J, Sachinidis A, Schwender H - PLoS ONE (2015)

Histogram of p-values (-log2 scale) calculated for TFBSs of clustered gene groups vs random groups of genes of the same size.TFBS overrepresentation p-values for clustered gene groups are shown as impulses, for random groups—as lines. According to this comparison, TFBSs assigned to the group with overrepresentation p-value less than 10−9 (log2P<-29.9) can be considered to be less likely to appear by a chance.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608779&req=5

pone.0140803.g005: Histogram of p-values (-log2 scale) calculated for TFBSs of clustered gene groups vs random groups of genes of the same size.TFBS overrepresentation p-values for clustered gene groups are shown as impulses, for random groups—as lines. According to this comparison, TFBSs assigned to the group with overrepresentation p-value less than 10−9 (log2P<-29.9) can be considered to be less likely to appear by a chance.
Mentions: Groups of genes derived by clustering are assigned TFBSs, whose presence on the promoters has low p-values. In addition to calculating these p-values, indicating significance of single TFBSs for regulation of these gene groups, we performed a separate test to check if our clustered gene groups show TFBS enrichment better than random groups of genes of the same size. These checks are necessary because of the multiple testing nature of TFBS assignments, when even randomly chosen groups can have certain TFBSs assigned a low p-value. The results are shown in Fig 5. Indeed, our groups have assigned TFBSs with far smaller p-values than the random groups, i.e. within this approach we cannot only examine general similarity of the promoters in terms of TFBSs, but also assign TFBSs, which may be relevant to the regulation of particular groups.

Bottom Line: Many development features were found to be conserved, and a majority of differentially regulated genes have similar expression change in both organisms.However, we also found that some biological processes develop differently; this can clearly be shown, for example, for neuron and sensory organ development.We also detected a larger number of upregulated genes during development of mESCs as compared to hESCs.

View Article: PubMed Central - PubMed

Affiliation: Center for Bioinformatics and Biostatistics, Biological Medical Research Center, Heinrich Heine University, Universitätsstrasse 1, 40225 Düsseldorf, Germany.

ABSTRACT
We performed a systematic analysis of gene expression features in early (10-21 days) development of human vs mouse embryonic cells (hESCs vs mESCs). Many development features were found to be conserved, and a majority of differentially regulated genes have similar expression change in both organisms. The similarity is especially evident, when gene expression profiles are clustered together and properties of clustered groups of genes are compared. First 10 days of mESC development match the features of hESC development within 21 days, in accordance with the differences in population doubling time in human and mouse ESCs. At the same time, several important differences are seen. There is a clear difference in initial expression change of transcription factors and stimulus responsive genes, which may be caused by the difference in experimental procedures. However, we also found that some biological processes develop differently; this can clearly be shown, for example, for neuron and sensory organ development. Some groups of genes show peaks of the expression levels during the development and these peaks cannot be claimed to happen at the same time points in the two organisms, as well as for the same groups of (orthologous) genes. We also detected a larger number of upregulated genes during development of mESCs as compared to hESCs. The differences were quantified by comparing promoters of related genes. Most of gene groups behave similarly and have similar transcription factor (TF) binding sites on their promoters. A few groups of genes have similar promoters, but are expressed differently in two species. Interestingly, there are groups of genes expressed similarly, although they have different promoters, which can be shown by comparing their TF binding sites. Namely, a large group of similarly expressed cell cycle-related genes is found to have discrepant TF binding properties in mouse vs human.

No MeSH data available.


Related in: MedlinePlus