Oral Presentation 39th Annual Lorne Genome Conference 2018

Developing iPSCs as a model for primate evolutionary genomics (#39)

Irene Gallego Romero 1
  1. University of Melbourne, Parkville, VIC, Australia

Functional genomics studies in primates have been consistently hindered due to the logistic and ethical limitations of obtaining samples – especially in the case of the critically endangered great apes, humanity's closest living relatives. But if we wish to truly understand the molecular background of human-unique traits, it is essential that we address these constraints. Reprogramming of somatic cell lines into induced pluripotent cell lines (iPSCs) from non-human primates, and their subsequent differentiation into otherwise unobservable tissue types, provides a transformative and highly versatile model system with which to examine the contributions recent gene regulatory change has made to our species. We have previously generated a panel of chimpanzee (Pan troglodytes) iPSCs and thoroughly characterised their transcriptional and regulatory landscape, as well as the effects of reprogramming on gene expression. We find that expression and regulatory variation in iPSCs is consistently constrained relative to the somatic tissues we reprogrammed the cells from, and inter-species differences attenuated in magnitude, suggesting this state is highly conserved between the two species. I will also present preliminary data from targeted differentiation experiments which suggest that iPSCs are a viable method for identifying functional interspecies differences – and the molecular mechanisms that underlie them – but that on occasion a combination of batch and donor effects can overpower relevant trends. Taken together our findings illustrate both the promise and limitations of using this iPSC-modelling paradigm for interspecies comparisons.