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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

Number of gene groups with binding site of TF.Correlation between the number of gene groups/clusters, having statistically significant overrepresentation of binding sites of 81 TFs, calculated for human and mouse clusters. The points are randomly disposed. The line y = 2 x is drawn for a reference.
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pone.0140803.g007: Number of gene groups with binding site of TF.Correlation between the number of gene groups/clusters, having statistically significant overrepresentation of binding sites of 81 TFs, calculated for human and mouse clusters. The points are randomly disposed. The line y = 2 x is drawn for a reference.

Mentions: Alone the ability of clustering approach to detect co-regulation is out of suspect, since using clustering we find many clusters with clearly assigned TFBSs (Table 3, last column). The lists of all TFs are given in S10 Table; altogether there are 81 TFs that can be called to be responsible for regulation of the development process. S10 Table also shows the number of gene groups (clusters), which are found to be regulated by given TFs. Some TFs appear to regulate many gene groups, for example, Sp1-4, Znf219, Patz1 (POZ-, AT hook-, and zinc finger-containing protein 1), EGR* (Early growth factors), Fox* (Forkhead box proteins), Wt1 (Wilms tumor protein), Tfdp1 (Transcription factor Dp-1), Tfap2 (Transcription factor AP-2 alpha), E2F*, Nrf1 (Nuclear respiratory factor 1), Znf148, Vdr (calcitriol receptor) can be associated with more than 5 clusters (either in mouse or human). Interestingly, the number of clusters, which TFs can regulate, is highly correlated between human and mouse (Pearson correlation coefficient 0.75, see Fig 7), probably showing that ubiquitous TFs are the same in human and mouse. However, human TFs regulate larger number of different clusters, than mouse TFs. It should also be noted that none of undifferentiated ESC-related TFs (OCT4, SOX2, and NANOG) is found to contribute to the regulation: all these are uniformly down-regulated during the development process.


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)

Number of gene groups with binding site of TF.Correlation between the number of gene groups/clusters, having statistically significant overrepresentation of binding sites of 81 TFs, calculated for human and mouse clusters. The points are randomly disposed. The line y = 2 x is drawn for a reference.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140803.g007: Number of gene groups with binding site of TF.Correlation between the number of gene groups/clusters, having statistically significant overrepresentation of binding sites of 81 TFs, calculated for human and mouse clusters. The points are randomly disposed. The line y = 2 x is drawn for a reference.
Mentions: Alone the ability of clustering approach to detect co-regulation is out of suspect, since using clustering we find many clusters with clearly assigned TFBSs (Table 3, last column). The lists of all TFs are given in S10 Table; altogether there are 81 TFs that can be called to be responsible for regulation of the development process. S10 Table also shows the number of gene groups (clusters), which are found to be regulated by given TFs. Some TFs appear to regulate many gene groups, for example, Sp1-4, Znf219, Patz1 (POZ-, AT hook-, and zinc finger-containing protein 1), EGR* (Early growth factors), Fox* (Forkhead box proteins), Wt1 (Wilms tumor protein), Tfdp1 (Transcription factor Dp-1), Tfap2 (Transcription factor AP-2 alpha), E2F*, Nrf1 (Nuclear respiratory factor 1), Znf148, Vdr (calcitriol receptor) can be associated with more than 5 clusters (either in mouse or human). Interestingly, the number of clusters, which TFs can regulate, is highly correlated between human and mouse (Pearson correlation coefficient 0.75, see Fig 7), probably showing that ubiquitous TFs are the same in human and mouse. However, human TFs regulate larger number of different clusters, than mouse TFs. It should also be noted that none of undifferentiated ESC-related TFs (OCT4, SOX2, and NANOG) is found to contribute to the regulation: all these are uniformly down-regulated during the development process.

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