Project description:Understanding cellular and molecular differences between human and non-human primates (NHPs) is essential to the basic comprehension of the evolution and diversity of our own species. Until now, preserved tissues have been the main source of most comparative studies between humans, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). However, these tissue samples do not fairly represent the distinctive traits of live cell behavior, are not amenable to genetic manipulation and do not allow translation of observed differences into phenotypical divergence. We hypothesized that induced pluripotent stem cells (iPSCs) could provide a unique biological resource to elucidate relevant phenotypical differences between human and the great apes and that those differences could have potential adaptation and speciation value. Here, we describe the generation and initial characterization of iPSCs from chimpanzees and bonobos as novel tools to explore our most recent evolution. Comparative gene expression analysis of human and NHP iPSCs revealed differences in regulation of Long Interspersed Nuclear Element (LINE-1 or L1) transposons. A force of change in mammalian evolution, L1 elements are retrotransposons that have remained active during primate evolution. We observed decreased levels of L1 restricting factors APOBEC3B (A3B)7 and PIWIL28 in NHP iPSCs which was correlated with increased human and chimpanzee L1 mobility and endogenous L1 mRNA levels. Moreover, results from manipulation of A3B and PIWIL2 levels in iPSCs suggested a causal inverse relationship between levels of these proteins and L1 activity. Finally, we found increased copy numbers of species-specific L1 elements in the genome of chimpanzees compared to humans, supporting the idea that increased L1 mobility in NHPs is not limited to iPSCs in culture and may have also occurred in the germline during primate evolution. We propose that differences in L1 mobility may have differentially shaped the genomes of humans and NHPs and could have had an adaptive significance. polyA RNA-Seq profiling of iPS cells from human, chimpanzee, and bonobo, and small RNA-Seq profiling of human iPS cells.

Project description:Gene expression profiling is an important tool in the development of medical countermeasures against chemical warfare agents (CWAs). Non-human primates (NHPs), specifically the rhesus macaque (Macaca mulatta), the cynomologus macaque (Macaca fascicularis) and the African green monkey (Chlorocebus aethiops), are vital models in the development of CWA prophylactics, therapeutics, and diagnostics. However, gene expression profiling of these NHPs is complicated by the fact their genomes are not completely sequenced, and that no commercially available oligonucleotide microarrays (genechips) exist. We, therefore, sought to determine whether gene expression profiling of NHPs could be performed using human genechips. Whole blood RNA was isolated from each species and used to generate genechip probes. Hybridization of the NHP samples to human genechips (Affymetrix Human U133 Plus 2.0) resulted in comparable numbers of transcripts detected compared with human samples. Statistical analysis revealed intraspecies reproducibility of genechip quality control metrics; interspecies comparison between NHPs and humans showed little significant difference in the quality and reproducibility of data generated using human genechips. Expression profiles of each species were compared using principal component analysis (PCA) and hierarchical clustering to determine the similarity of the expression profiles within and across the species. The cynomologus group showed the least intraspecies variability, while the human group showed the greatest intraspecies variability. Intraspecies comparison of the expression profiles identified probesets that were reproducibly detected within each species. Each NHP species was found to be dissimilar to humans; the cynomologus group was the most dissimilar. Interspecies comparison of the expression profiles revealed probesets that were reproducibly detected in all species examined. These results show that human genechips can be used for expression profiling of NHP samples and provide a foundation for the development of tools for comparing human and NHP gene expression profiles. Keywords = human Keywords = homo sapien Keywords = blood Keywords = rhesus macaque Keywords = cynomologus macaque Keywords = African green monkey Keywords: parallel sample

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Differential LINE-1 retrotransposition in induced pluripotent stem cells between humans and great apes

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