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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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Related in: MedlinePlus

Heatmap of evidence for enrichment of GOBP terms in target aggregates.Aggregation of the twelve comparisons into target aggregates was performed as described in the text. The heatmap includes only GOBP terms for which a significant enrichment in one of the block aggregates was determined using our statistical assessment. This aggregate is colour-coded to the left of the heatmap (green: naïve, red: primed, blue: NHPM).
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f6: Heatmap of evidence for enrichment of GOBP terms in target aggregates.Aggregation of the twelve comparisons into target aggregates was performed as described in the text. The heatmap includes only GOBP terms for which a significant enrichment in one of the block aggregates was determined using our statistical assessment. This aggregate is colour-coded to the left of the heatmap (green: naïve, red: primed, blue: NHPM).

Mentions: We performed a third noise reduction and data aggregation step and combined the GOBP enrichment data. More specifically, we summarized the evidence for enrichment of GOBP terms for each target condition (see Methods). The resulting matrix of aggregated evidence was again subjected to a number of analyses. First, we generated a heatmap of the matrix (Figure 6). Clustering of the target aggregates (columns) results in two clusters, one of them containing the target aggregates that describe the naïve pluripotent state in human and mouse, while the other one comprises the corresponding aggregates for the primed state. This representation of the data therefore strengthens the case for a similarity between the prototypical naïve mouse and the naïve human states, as proposed by ref. 9. This clustering is restricted to the GOBP terms that were found to be specific for any of the block aggregates, as detailed below.


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)

Heatmap of evidence for enrichment of GOBP terms in target aggregates.Aggregation of the twelve comparisons into target aggregates was performed as described in the text. The heatmap includes only GOBP terms for which a significant enrichment in one of the block aggregates was determined using our statistical assessment. This aggregate is colour-coded to the left of the heatmap (green: naïve, red: primed, blue: NHPM).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Heatmap of evidence for enrichment of GOBP terms in target aggregates.Aggregation of the twelve comparisons into target aggregates was performed as described in the text. The heatmap includes only GOBP terms for which a significant enrichment in one of the block aggregates was determined using our statistical assessment. This aggregate is colour-coded to the left of the heatmap (green: naïve, red: primed, blue: NHPM).
Mentions: We performed a third noise reduction and data aggregation step and combined the GOBP enrichment data. More specifically, we summarized the evidence for enrichment of GOBP terms for each target condition (see Methods). The resulting matrix of aggregated evidence was again subjected to a number of analyses. First, we generated a heatmap of the matrix (Figure 6). Clustering of the target aggregates (columns) results in two clusters, one of them containing the target aggregates that describe the naïve pluripotent state in human and mouse, while the other one comprises the corresponding aggregates for the primed state. This representation of the data therefore strengthens the case for a similarity between the prototypical naïve mouse and the naïve human states, as proposed by ref. 9. This clustering is restricted to the GOBP terms that were found to be specific for any of the block aggregates, as detailed below.

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