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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

All pairwise comparisons of conditions, and aggregates thereof.A comparison has a source and a target condition. For example, for comparison #1, NH is the source and NM is the target condition. Aggregates of comparisons are defined as follows. (a) by target condition (NH, NM, PH, PM), and (b) block-wise. The latter are subdivided into the natural blocks naïve (N, green) and primed (P, red) and the mixed ones NHPM (blue) and NMPH (cyan), see also Supplementary Table S1. Target aggregates are indicated by arrows below the columns; all comparisons within a column constitute a single target aggregate. Block aggregates are indicated by enclosing coloured circles and rounded rectangles. All comparisons that are enclosed within a shape of a given colour are part of the aggregate that is associated with that colour; a comparison may be part of multiple aggregates. For example, N (green) aggregates comparisons with target naïve (regardless of species, but excluding naïve as the source), NH aggregates all comparisons with target NH, and NHPM allows checking the hypothesis that NH and PM have properties in common. LinkScore calculations for a comparison estimate which links between genes start up during the transition from source to target. For each comparison, the top-scoring links form its link set, which in turn gives rise to a corresponding gene set.
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f3: All pairwise comparisons of conditions, and aggregates thereof.A comparison has a source and a target condition. For example, for comparison #1, NH is the source and NM is the target condition. Aggregates of comparisons are defined as follows. (a) by target condition (NH, NM, PH, PM), and (b) block-wise. The latter are subdivided into the natural blocks naïve (N, green) and primed (P, red) and the mixed ones NHPM (blue) and NMPH (cyan), see also Supplementary Table S1. Target aggregates are indicated by arrows below the columns; all comparisons within a column constitute a single target aggregate. Block aggregates are indicated by enclosing coloured circles and rounded rectangles. All comparisons that are enclosed within a shape of a given colour are part of the aggregate that is associated with that colour; a comparison may be part of multiple aggregates. For example, N (green) aggregates comparisons with target naïve (regardless of species, but excluding naïve as the source), NH aggregates all comparisons with target NH, and NHPM allows checking the hypothesis that NH and PM have properties in common. LinkScore calculations for a comparison estimate which links between genes start up during the transition from source to target. For each comparison, the top-scoring links form its link set, which in turn gives rise to a corresponding gene set.

Mentions: For each possible pair of source and target conditions (Figure 3), we selected the links with LinkScores at or above the 99.75 percentile, yielding twelve link sets. We then extracted from each link set the genes that are connected by those links, yielding twelve gene sets, hypothesizing that these genes are involved in the major mechanisms characterizing the transition to the respective target condition.


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)

All pairwise comparisons of conditions, and aggregates thereof.A comparison has a source and a target condition. For example, for comparison #1, NH is the source and NM is the target condition. Aggregates of comparisons are defined as follows. (a) by target condition (NH, NM, PH, PM), and (b) block-wise. The latter are subdivided into the natural blocks naïve (N, green) and primed (P, red) and the mixed ones NHPM (blue) and NMPH (cyan), see also Supplementary Table S1. Target aggregates are indicated by arrows below the columns; all comparisons within a column constitute a single target aggregate. Block aggregates are indicated by enclosing coloured circles and rounded rectangles. All comparisons that are enclosed within a shape of a given colour are part of the aggregate that is associated with that colour; a comparison may be part of multiple aggregates. For example, N (green) aggregates comparisons with target naïve (regardless of species, but excluding naïve as the source), NH aggregates all comparisons with target NH, and NHPM allows checking the hypothesis that NH and PM have properties in common. LinkScore calculations for a comparison estimate which links between genes start up during the transition from source to target. For each comparison, the top-scoring links form its link set, which in turn gives rise to a corresponding gene set.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: All pairwise comparisons of conditions, and aggregates thereof.A comparison has a source and a target condition. For example, for comparison #1, NH is the source and NM is the target condition. Aggregates of comparisons are defined as follows. (a) by target condition (NH, NM, PH, PM), and (b) block-wise. The latter are subdivided into the natural blocks naïve (N, green) and primed (P, red) and the mixed ones NHPM (blue) and NMPH (cyan), see also Supplementary Table S1. Target aggregates are indicated by arrows below the columns; all comparisons within a column constitute a single target aggregate. Block aggregates are indicated by enclosing coloured circles and rounded rectangles. All comparisons that are enclosed within a shape of a given colour are part of the aggregate that is associated with that colour; a comparison may be part of multiple aggregates. For example, N (green) aggregates comparisons with target naïve (regardless of species, but excluding naïve as the source), NH aggregates all comparisons with target NH, and NHPM allows checking the hypothesis that NH and PM have properties in common. LinkScore calculations for a comparison estimate which links between genes start up during the transition from source to target. For each comparison, the top-scoring links form its link set, which in turn gives rise to a corresponding gene set.
Mentions: For each possible pair of source and target conditions (Figure 3), we selected the links with LinkScores at or above the 99.75 percentile, yielding twelve link sets. We then extracted from each link set the genes that are connected by those links, yielding twelve gene sets, hypothesizing that these genes are involved in the major mechanisms characterizing the transition to the respective target condition.

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