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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

Roadmap of the work presented in this paper.We start by integrating several input data sets, namely one large-scale network of direct (physical) and indirect (functional) interactions derived from STRING and featuring mostly expert-curated data, and two high-throughput transcriptomics studies that describe the transition between naïve and primed pluripotency in human and mouse. On this multidimensional data set, we sequentially apply computational methods (grey elliptical boxes), obtaining data in a more and more abstract form, from genes to mechanisms to gene ontology terms. Each step is intended to remove noise from the data. The result of each step is shown in a blue box. We employed several analysis and visualization methods to obtain insights into the data at each step (beige boxes).
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f1: Roadmap of the work presented in this paper.We start by integrating several input data sets, namely one large-scale network of direct (physical) and indirect (functional) interactions derived from STRING and featuring mostly expert-curated data, and two high-throughput transcriptomics studies that describe the transition between naïve and primed pluripotency in human and mouse. On this multidimensional data set, we sequentially apply computational methods (grey elliptical boxes), obtaining data in a more and more abstract form, from genes to mechanisms to gene ontology terms. Each step is intended to remove noise from the data. The result of each step is shown in a blue box. We employed several analysis and visualization methods to obtain insights into the data at each step (beige boxes).

Mentions: We set out to describe the transition between the naïve and the primed state of pluripotent stem cells in two mammalian species, human and mouse. The comparison is based on biological mechanisms that we define by the joint analysis of transcriptomics and network data. A roadmap to our approach is presented in Figure 1; see Methods for details.


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)

Roadmap of the work presented in this paper.We start by integrating several input data sets, namely one large-scale network of direct (physical) and indirect (functional) interactions derived from STRING and featuring mostly expert-curated data, and two high-throughput transcriptomics studies that describe the transition between naïve and primed pluripotency in human and mouse. On this multidimensional data set, we sequentially apply computational methods (grey elliptical boxes), obtaining data in a more and more abstract form, from genes to mechanisms to gene ontology terms. Each step is intended to remove noise from the data. The result of each step is shown in a blue box. We employed several analysis and visualization methods to obtain insights into the data at each step (beige boxes).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Roadmap of the work presented in this paper.We start by integrating several input data sets, namely one large-scale network of direct (physical) and indirect (functional) interactions derived from STRING and featuring mostly expert-curated data, and two high-throughput transcriptomics studies that describe the transition between naïve and primed pluripotency in human and mouse. On this multidimensional data set, we sequentially apply computational methods (grey elliptical boxes), obtaining data in a more and more abstract form, from genes to mechanisms to gene ontology terms. Each step is intended to remove noise from the data. The result of each step is shown in a blue box. We employed several analysis and visualization methods to obtain insights into the data at each step (beige boxes).
Mentions: We set out to describe the transition between the naïve and the primed state of pluripotent stem cells in two mammalian species, human and mouse. The comparison is based on biological mechanisms that we define by the joint analysis of transcriptomics and network data. A roadmap to our approach is presented in Figure 1; see Methods for details.

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