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Comparative computational analysis of pluripotency in human and mouse stem cells

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...

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Autores principales: Ernst, Mathias, Dawud, Raed Abu, Kurtz, Andreas, Schotta, Gunnar, Taher, Leila, Fuellen, Georg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300513/
https://www.ncbi.nlm.nih.gov/pubmed/25604210
http://dx.doi.org/10.1038/srep07927
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author Ernst, Mathias
Dawud, Raed Abu
Kurtz, Andreas
Schotta, Gunnar
Taher, Leila
Fuellen, Georg
author_facet Ernst, Mathias
Dawud, Raed Abu
Kurtz, Andreas
Schotta, Gunnar
Taher, Leila
Fuellen, Georg
author_sort Ernst, Mathias
collection PubMed
description 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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spelling pubmed-43005132015-01-27 Comparative computational analysis of pluripotency in human and mouse stem cells Ernst, Mathias Dawud, Raed Abu Kurtz, Andreas Schotta, Gunnar Taher, Leila Fuellen, Georg Sci Rep Article 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. Nature Publishing Group 2015-01-21 /pmc/articles/PMC4300513/ /pubmed/25604210 http://dx.doi.org/10.1038/srep07927 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Article
Ernst, Mathias
Dawud, Raed Abu
Kurtz, Andreas
Schotta, Gunnar
Taher, Leila
Fuellen, Georg
Comparative computational analysis of pluripotency in human and mouse stem cells
title Comparative computational analysis of pluripotency in human and mouse stem cells
title_full Comparative computational analysis of pluripotency in human and mouse stem cells
title_fullStr Comparative computational analysis of pluripotency in human and mouse stem cells
title_full_unstemmed Comparative computational analysis of pluripotency in human and mouse stem cells
title_short Comparative computational analysis of pluripotency in human and mouse stem cells
title_sort comparative computational analysis of pluripotency in human and mouse stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300513/
https://www.ncbi.nlm.nih.gov/pubmed/25604210
http://dx.doi.org/10.1038/srep07927
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