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Comparative computational analysis of pluripotency in human and mouse stem cells.

Ernst M, Abu Dawud R, Kurtz A, Schotta G, Taher L, Fuellen G - Sci Rep (2015)

Bottom Line: Pluripotent cells can be subdivided into two distinct states, the naïve and the primed state, the latter being further advanced on the path of differentiation.Reprogramming of human stem cells into a more naïve-like state is an important research focus.The pipeline consists of identifying regulated start-ups/shut-downs in terms of molecular interactions, followed by functional annotation of the genes involved and aggregation of results across conditions, yielding sets of mechanisms that are consistently regulated in transitions towards similar states of pluripotency.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany.

ABSTRACT
Pluripotent cells can be subdivided into two distinct states, the naïve and the primed state, the latter being further advanced on the path of differentiation. There are substantial differences in the regulation of pluripotency between human and mouse, and in humans only stem cells that resemble the primed state in mouse are readily available. Reprogramming of human stem cells into a more naïve-like state is an important research focus. Here, we developed a pipeline to reanalyze transcriptomics data sets that describe both states, naïve and primed pluripotency, in human and mouse. The pipeline consists of identifying regulated start-ups/shut-downs in terms of molecular interactions, followed by functional annotation of the genes involved and aggregation of results across conditions, yielding sets of mechanisms that are consistently regulated in transitions towards similar states of pluripotency. Our results suggest that one published protocol for naïve human cells gave rise to human cells that indeed share putative mechanisms with the prototypical naïve mouse pluripotent cells, such as DNA damage response and histone acetylation. However, cellular response and differentiation-related mechanisms are similar between the naïve human state and the primed mouse state, so the naïve human state did not fully reflect the naïve mouse state.

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Analysis of the combined gene expression data set of Hanna et al (2009, 2010).The Hanna/Hanna data set consists of 25 microarray samples that correspond to the four conditions naïvehuman (NH), primedhuman (PH), naïvemouse (NM), and primedmouse (PM). For the sample preprocessing and construction of the gene expression matrix, see text. A: Hierarchical clustering dendrogram of the samples (Spearman's rank correlation, complete linkage). The colour bar below the dendrogram provides information about the species (upper bar) and the pluripotency state (lower bar) of the single samples. The samples are labelled with their GEO identifiers; see data sets GSE21222 and GSE15603 for further details. B: Principal component analysis (PCA) of the data set. Four distinct clusters are identifiable, which correspond to the four conditions. The species of origin of the samples is indicated by the colour of the single symbols, while the colour of the ellipses enclosing the four clusters indicates the pluripotency state of the samples inside.
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f2: Analysis of the combined gene expression data set of Hanna et al (2009, 2010).The Hanna/Hanna data set consists of 25 microarray samples that correspond to the four conditions naïvehuman (NH), primedhuman (PH), naïvemouse (NM), and primedmouse (PM). For the sample preprocessing and construction of the gene expression matrix, see text. A: Hierarchical clustering dendrogram of the samples (Spearman's rank correlation, complete linkage). The colour bar below the dendrogram provides information about the species (upper bar) and the pluripotency state (lower bar) of the single samples. The samples are labelled with their GEO identifiers; see data sets GSE21222 and GSE15603 for further details. B: Principal component analysis (PCA) of the data set. Four distinct clusters are identifiable, which correspond to the four conditions. The species of origin of the samples is indicated by the colour of the single symbols, while the colour of the ellipses enclosing the four clusters indicates the pluripotency state of the samples inside.

Mentions: Expression profiles from human and mouse stem cells were combined into one data set (see Methods) and we will refer to this and the analysis based thereon as the Hanna/Hanna data and the Hanna/Hanna analysis. Our preprocessing protocol resulted in a combined data set comprising 25 samples and approximately 11,000 genes. Samples belong to one of four conditions: naïvehuman (NH, n = 6), primedhuman (PH, n = 5), naïvemouse (NM, n = 6), and primedmouse (PM, n = 8). Hierarchical clustering of this data set separates the samples according to their pluripotency state (Figure 2A), in agreement with ref. 9. A principal component analysis (PCA) supports the conclusion drawn from the clustering (Figure 2B). However, the second principal component (PC) indicates that there may be some similarity between NH and PM, on which we will follow up upon later.


Comparative computational analysis of pluripotency in human and mouse stem cells.

Ernst M, Abu Dawud R, Kurtz A, Schotta G, Taher L, Fuellen G - Sci Rep (2015)

Analysis of the combined gene expression data set of Hanna et al (2009, 2010).The Hanna/Hanna data set consists of 25 microarray samples that correspond to the four conditions naïvehuman (NH), primedhuman (PH), naïvemouse (NM), and primedmouse (PM). For the sample preprocessing and construction of the gene expression matrix, see text. A: Hierarchical clustering dendrogram of the samples (Spearman's rank correlation, complete linkage). The colour bar below the dendrogram provides information about the species (upper bar) and the pluripotency state (lower bar) of the single samples. The samples are labelled with their GEO identifiers; see data sets GSE21222 and GSE15603 for further details. B: Principal component analysis (PCA) of the data set. Four distinct clusters are identifiable, which correspond to the four conditions. The species of origin of the samples is indicated by the colour of the single symbols, while the colour of the ellipses enclosing the four clusters indicates the pluripotency state of the samples inside.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4300513&req=5

f2: Analysis of the combined gene expression data set of Hanna et al (2009, 2010).The Hanna/Hanna data set consists of 25 microarray samples that correspond to the four conditions naïvehuman (NH), primedhuman (PH), naïvemouse (NM), and primedmouse (PM). For the sample preprocessing and construction of the gene expression matrix, see text. A: Hierarchical clustering dendrogram of the samples (Spearman's rank correlation, complete linkage). The colour bar below the dendrogram provides information about the species (upper bar) and the pluripotency state (lower bar) of the single samples. The samples are labelled with their GEO identifiers; see data sets GSE21222 and GSE15603 for further details. B: Principal component analysis (PCA) of the data set. Four distinct clusters are identifiable, which correspond to the four conditions. The species of origin of the samples is indicated by the colour of the single symbols, while the colour of the ellipses enclosing the four clusters indicates the pluripotency state of the samples inside.
Mentions: Expression profiles from human and mouse stem cells were combined into one data set (see Methods) and we will refer to this and the analysis based thereon as the Hanna/Hanna data and the Hanna/Hanna analysis. Our preprocessing protocol resulted in a combined data set comprising 25 samples and approximately 11,000 genes. Samples belong to one of four conditions: naïvehuman (NH, n = 6), primedhuman (PH, n = 5), naïvemouse (NM, n = 6), and primedmouse (PM, n = 8). Hierarchical clustering of this data set separates the samples according to their pluripotency state (Figure 2A), in agreement with ref. 9. A principal component analysis (PCA) supports the conclusion drawn from the clustering (Figure 2B). However, the second principal component (PC) indicates that there may be some similarity between NH and PM, on which we will follow up upon later.

Bottom Line: Pluripotent cells can be subdivided into two distinct states, the naïve and the primed state, the latter being further advanced on the path of differentiation.Reprogramming of human stem cells into a more naïve-like state is an important research focus.The pipeline consists of identifying regulated start-ups/shut-downs in terms of molecular interactions, followed by functional annotation of the genes involved and aggregation of results across conditions, yielding sets of mechanisms that are consistently regulated in transitions towards similar states of pluripotency.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany.

ABSTRACT
Pluripotent cells can be subdivided into two distinct states, the naïve and the primed state, the latter being further advanced on the path of differentiation. There are substantial differences in the regulation of pluripotency between human and mouse, and in humans only stem cells that resemble the primed state in mouse are readily available. Reprogramming of human stem cells into a more naïve-like state is an important research focus. Here, we developed a pipeline to reanalyze transcriptomics data sets that describe both states, naïve and primed pluripotency, in human and mouse. The pipeline consists of identifying regulated start-ups/shut-downs in terms of molecular interactions, followed by functional annotation of the genes involved and aggregation of results across conditions, yielding sets of mechanisms that are consistently regulated in transitions towards similar states of pluripotency. Our results suggest that one published protocol for naïve human cells gave rise to human cells that indeed share putative mechanisms with the prototypical naïve mouse pluripotent cells, such as DNA damage response and histone acetylation. However, cellular response and differentiation-related mechanisms are similar between the naïve human state and the primed mouse state, so the naïve human state did not fully reflect the naïve mouse state.

Show MeSH
Related in: MedlinePlus