title: Comparative computational analysis of pluripotency in human and mouse stem cells.
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.
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Ernst
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité, Berlin, Germany.
authors.forename: Raed
authors.initials: R
authors.lastname: Abu Dawud
authors.affiliation: 1] Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité, Berlin, Germany [2] College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kurtz
authors.affiliation: Ludwig Maximilians University and Munich Center for Integrated Protein Science (CiPSM), Adolf-Butenandt-Institute, Munich, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Schotta
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany.
authors.forename: Leila
authors.initials: L
authors.lastname: Taher
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Fuellen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D003198:Computer Simulation; D004249:DNA Damage; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D013045:Species Specificity