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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

Relationship between the cell conditions in Gene Ontology space.Our method yields a visualization of the similarity of conditions together with the identification of the Gene Ontology biological processes that are underlying this similarity.
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f14: Relationship between the cell conditions in Gene Ontology space.Our method yields a visualization of the similarity of conditions together with the identification of the Gene Ontology biological processes that are underlying this similarity.

Mentions: In summary, we designed a workflow that allows the (re-)analysis of noisy gene expression data, employing several layers of abstraction. We re-analyzed data sets from naïve mouse and primed as well as naïve and primed human pluripotent stem cells and characterized the various cell types by enrichment analyses. We found that cells claimed to be naïvehuman display an overlapping gene expression signature with the naïvemouse cells, explaining their naïve properties. However, we also found similarities to the primed mouse state. This raises the question of what caused the incomplete induction of the naïve state in hESCs. Closely related are the biological processes causing hESCs to transit from the naïve into the primed state during their isolation, as they were naïve in the inner cell mass in the first place. As summarized in Figure 14, our study suggests that there are residual biological processes typically found in primed mouse pluripotency that hinder complete induction of true human naïvity. These processes include response to endogenous stimulus and differentiation-related biological processes, which may also be at work in the defaulting of hESCs into the primed state. Inhibiting these may enable us to come even closer to the naïve human pluripotent state.


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)

Relationship between the cell conditions in Gene Ontology space.Our method yields a visualization of the similarity of conditions together with the identification of the Gene Ontology biological processes that are underlying this similarity.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f14: Relationship between the cell conditions in Gene Ontology space.Our method yields a visualization of the similarity of conditions together with the identification of the Gene Ontology biological processes that are underlying this similarity.
Mentions: In summary, we designed a workflow that allows the (re-)analysis of noisy gene expression data, employing several layers of abstraction. We re-analyzed data sets from naïve mouse and primed as well as naïve and primed human pluripotent stem cells and characterized the various cell types by enrichment analyses. We found that cells claimed to be naïvehuman display an overlapping gene expression signature with the naïvemouse cells, explaining their naïve properties. However, we also found similarities to the primed mouse state. This raises the question of what caused the incomplete induction of the naïve state in hESCs. Closely related are the biological processes causing hESCs to transit from the naïve into the primed state during their isolation, as they were naïve in the inner cell mass in the first place. As summarized in Figure 14, our study suggests that there are residual biological processes typically found in primed mouse pluripotency that hinder complete induction of true human naïvity. These processes include response to endogenous stimulus and differentiation-related biological processes, which may also be at work in the defaulting of hESCs into the primed state. Inhibiting these may enable us to come even closer to the naïve human pluripotent state.

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