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.

Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance

“…System; Zeiss). Twenty-five nanograms total RNA were used to construct barcoded mRNA-Seq libraries that were sequenced on a Genome Analyzer IIx platform as described earlier (50). Gene expression analysis was performed by the multifactor model of the R package for differential expression analysis for sequence count data (51).…”

Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells

“…Another striking observation is that PSC models recapitulate faithfully the timing of developmental events, and in a speciesspecific way. PSCs thereby constitute promising tools to uncover and dissect the links between development and evolution, not only by comparing human and mouse PSC-derived systems, but also by implementing reprogramming of somatic cells of other mammalian species in which experimental manipulation in embryos is difficult, such as non-human primates (Wunderlich et al, 2014). This might shed further light on the evolutionary conservation and divergence of various other aspects of brain development, such as the gyration patterns of the cerebral cortex that have been independently acquired in multiple mammalian lineages (Lui et al, 2011).…”

Functional Divergence of the Nuclear ReceptorNR2C1as a Modulator of Pluripotentiality During Hominid Evolution

“…Finally, analysis of NR2C1 expression in the mouse embryo illustrates that it is robustly expressed in placodally derived neuroectodermal stem cells and presumptive neural-crest-derived mesenchymal stem cells . Further investigation as to whether this gene can regulate self-renewal and/or pluripotentiality in populations of stem cells other than ES cells such as in cultures of neural stem cells, or in iPSCs generated from nonhuman primates (Marchetto et al 2013;Wunderlich et al 2014;Gallego Romero et al 2015;Ramaswamy et al 2015) is warranted. iPSCs are an incredibly useful tool and provide a great deal of insight into questions of pluripotentiality and differentiation (Takahashi and Yamanaka 2006); however, some questions remain regarding whether epigenetic reprogramming during the iPSC protocol results in full pluripotency potential (Bilic and Belmonte 2012;Robinton and Daley 2012;Halevy and Urbach 2014).…”