Mitochondria-selective primate cell fusions reveal functional consequences of mitochondrial divergence

Interspecies composite cell lines (or hybrid cells) are powerful tools to study genomic divergence between species. However, to date, the only pluripotent composite lines to exist are between human and chimpanzee. In addition, while these human-chimp composite lines contain the nuclear genomes from both species, they only contain the mitochondrial genome from one: human. Here we describe the generation of multiple composite pluripotent stem cell (PSC) lines between human and all other species of great apes (chimpanzee [Pan troglodytes], bonobo [Pan paniscus], gorilla [Gorilla gorilla], and orangutan [Pongo abelii]). In addition, we utilized a strategy based on enforced mitophagy to generate human-great ape composite PSCs that contain either the human or the non-human primate (NHP) mitochondrial genomes. To compare composite PSCs harboring human mtDNA vs those that harbor NHP mtDNA by RNA-Seq.