Project description:Macaque species share over 93% genome homology with humans and develop many disease phenotypes similar to those of humans, making them valuable animal models for the study of human diseases (e.g.,HIV and neurodegenerative diseases). However, the quality of genome assembly and annotation for several macaque species lags behind the human genome effort. To close this gap and enhance functional genomics approaches, we employed a combination of de novo linked-read assembly and scaffolding using proximity ligation assay (HiC) to assemble the pig-tailed macaque (Macaca nemestrina) genome. This combinatorial method yielded large scaffolds at chromosome-level with a scaffold N50 of 127.5 Mb; the 23 largest scaffolds covered 90% of the entire genome. This assembly revealed large-scale rearrangements between pig-tailed macaque chromosomes 7, 12, and 13 and human chromosomes 2, 14, and 15. We subsequently annotated the genome using transcriptome and proteomics data from personalized induced pluripotent stem cells (iPSCs) derived from the same animal. Reconstruction of the evolutionary tree using whole genome annotation and orthologous comparisons among three macaque species, human and mouse genomes revealed extensive homology between human and pig-tailed macaques with regards to both pluripotent stem cell genes and innate immune gene pathways. Our results confirm that rhesus and cynomolgus macaques exhibit a closer evolutionary distance to each other than either species exhibits to humans or pig-tailed macaques. These findings demonstrate that pig-tailed macaques can serve as an excellent animal model for the study of many human diseases particularly with regards to pluripotency and innate immune pathways.
Project description:Macaca fascicularis (long-tailed, cynomolgus, or crab-eating macaque) is a highly advantageous model in which to study human cochlea with regard to both evolutionary proximity and physiological similarity of the auditory system. To better understand the properties of primate cochlear function, we analyzed the genes predominantly expressed in M. fascicularis cochlea.
Project description:Single-nucleus RNA sequencing (snRNA-seq) was used to profile the transcriptome of 7,631 nuclei in macaque adult testis. This dataset includes two samples from two different individuals. This dataset is part of a larger evolutionary study of adult testis at the single-nucleus level (97,521 single-nuclei in total) across mammals including 10 representatives of the three main mammalian lineages: human, chimpanzee, bonobo, gorilla, gibbon, rhesus macaque, marmoset, mouse (placental mammals); grey short-tailed opossum (marsupials); and platypus (egg-laying monotremes). Corresponding data were generated for a bird (red junglefowl, the progenitor of domestic chicken), to be used as an evolutionary outgroup.
Project description:Induced pluripotent stem cells (iPSCs) hold promise for generating personalized xenogenic organs via development of cross-species chimeric animals. However, whether human and other primate iPSCs are capable of establishing cross-species chimeras remains unknown. Recognizing the ethical concerns of cross-species chimerism using human iPSCs, we explored the capacity for cross-species chimerism between distinct, non-human primates. Injection of either pig-tailed macaque iPSCs or chimpanzee iPSCs into the rhesus macaque blastocyst embryos demonstrated that these cells survive, proliferate, and integrate near the rhesus inner cell mass (ICM). Ectopic expression of BCL2 in pig-tailed and chimpanzee iPSCs greatly improved the success rate of establishing cross-species blastocyst chimerism. This study represents the first successful cross-species blastocyst chimerism between distinct, non-human primate species, and highlights critical factors that may be necessary to unlock the broad potential of primate iPSCs to form cross-species chimeras, with diverse applications for basic research and translational medicine.