Insights from a chimpanzee adipose stromal cell population: opportunities for adult stem cells to expand primate functional genomics.
Bottom Line: Although hesitant to draw definitive conclusions from these data given the limited sample size, we wish to stress the opportunities that adult stem cells offer for studying primate evolution.In particular, adult stem cells provide a powerful means to investigate the profound disease susceptibilities unique to humans and a promising tool for conservation efforts with nonhuman primates.By allowing for experimental perturbations in relevant cell types, adult stem cells promise to complement classic comparative primate genomics based on in vivo sampling.
Affiliation: Department of Biology, Duke University.
Comparisons between humans and chimpanzees are essential for understanding traits unique to each species. However, linking important phenotypic differences to underlying molecular changes is often challenging. The ability to generate, differentiate, and profile adult stem cells provides a powerful but underutilized opportunity to investigate the molecular basis for trait differences between species within specific cell types and in a controlled environment. Here, we characterize adipose stromal cells (ASCs) from Clint, the chimpanzee whose genome was first sequenced. Using imaging and RNA-Seq, we compare the chimpanzee ASCs with three comparable human cell lines. Consistent with previous studies on ASCs in humans, the chimpanzee cells have fibroblast-like morphology and express genes encoding components of the extracellular matrix at high levels. Differentially expressed genes are enriched for distinct functional classes between species: immunity and protein processing are higher in chimpanzees, whereas cell cycle and DNA processing are higher in humans. Although hesitant to draw definitive conclusions from these data given the limited sample size, we wish to stress the opportunities that adult stem cells offer for studying primate evolution. In particular, adult stem cells provide a powerful means to investigate the profound disease susceptibilities unique to humans and a promising tool for conservation efforts with nonhuman primates. By allowing for experimental perturbations in relevant cell types, adult stem cells promise to complement classic comparative primate genomics based on in vivo sampling.
Mentions: To uncover functional differences between chimpanzee and human ASCs, we interrogated the red (chimpanzee higher) and blue (human higher) genes in figure 5B using the PANTHER tools database (Mi et al. 2005). These standard categorical enrichments include gene ontology (GO) biological processes, GO molecular functions, and PANTHER protein classes. Chimpanzee ASCs have higher expression for genes involved in immunity (dark red) and protein processing (light red), whereas human ASCs have higher expression for genes involved in the cell cycle (dark blue) and DNA processing (light blue) (fig. 6). Strikingly, every one of the broader highlighted categories is distributed perfectly onto either the human or chimpanzee branch (for instance, all six cell cycle subcategories are enriched on the human branch). The most significant enrichments for the chimpanzee are processes involved in the development and functioning of the immune system, which responds to potential invasive or internal threats (fig. 6) (Gene Ontology Consortium 2000). A previous study also found that ASCs are enriched for immune-related expression when compared with other stem cells populations (Jansen et al. 2010). Another complementary category that is enriched in the chimpanzee and significantly depauperate in humans is cytokine activity (fig. 6). The chemokines, one class of cytokines, elicit homing behavior in bone marrow stem cells by sensing tissue injury and migrating to the site of damage (Shyu et al. 2006). Higher expression of genes involved in immunity and cytokine activity is consistent with anecdotal evidence that both captive and wild chimpanzees have faster epidermal wound healing abilities compared with humans (Hedlund et al. 2007). These results provide a glimpse into the molecular differences underlying the human and chimpanzee condition.Fig. 6.—