title: Primate iPS cells as tools for evolutionary analyses.
abstract: Induced pluripotent stem cells (iPSCs) are regarded as a central tool to understand human biology in health and disease. Similarly, iPSCs from non-human primates should be a central tool to understand human evolution, in particular for assessing the conservation of regulatory networks in iPSC models. Here, we have generated human, gorilla, bonobo and cynomolgus monkey iPSCs and assess their usefulness in such a framework. We show that these cells are well comparable in their differentiation potential and are generally similar to human, cynomolgus and rhesus monkey embryonic stem cells (ESCs). RNA sequencing reveals that expression differences among clones, individuals and stem cell type are all of very similar magnitude within a species. In contrast, expression differences between closely related primate species are three times larger and most genes show significant expression differences among the analyzed species. However, pseudogenes differ more than twice as much, suggesting that evolution of expression levels in primate stem cells is rapid, but constrained. These patterns in pluripotent stem cells are comparable to those found in other tissues except testis. Hence, primate iPSCs reveal insights into general primate gene expression evolution and should provide a rich source to identify conserved and species-specific gene expression patterns for cellular phenotypes.
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany; REBIRTH-Cluster of Excellence, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wunderlich
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kircher
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany; Department Biology II, Ludwig Maximilian University Munich, D-82152 Martinsried, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Vieth
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany; REBIRTH-Cluster of Excellence, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Haase
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany; REBIRTH-Cluster of Excellence, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Merkert
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany; REBIRTH-Cluster of Excellence, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Beier
authors.affiliation: Department Cell and Molecular Pathology, Hannover Medical School, 30625 Hannover, Germany; REBIRTH-Cluster of Excellence, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.affiliation: Institute for Laboratory Animal Science, Hannover Medical School, 30625 Hannover, Germany; REBIRTH-Cluster of Excellence, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Glage
authors.affiliation: Department of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany; REBIRTH-Cluster of Excellence, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.affiliation: Washington National Primate Research Center, Seattle, USA.
authors.forename: Eliza C
authors.initials: EC
authors.lastname: Curnow
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany.
authors.forename: Svante
authors.initials: S
authors.lastname: Pääbo
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany; REBIRTH-Cluster of Excellence, Germany. Electronic address: martin.ulrich@mh-hannover.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Martin
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany; Department Biology II, Ludwig Maximilian University Munich, D-82152 Martinsried, Germany. Electronic address: enard@bio.lmu.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Enard
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002454:Cell Differentiation; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011323:Primates