Differentiation of iPSCs into Hematopoietic Stem and Progenitor Cells (HSPCs) across human, chimpanzee, and pig-tailed macaque

Induced pluripotent stem cells (iPSCs) are powerful tools for in vitro generation of different cell types including hematopoietic (blood-forming) stem and progenitor cells (HSPCs). iPSCs provide a controlled platform to compare cell differentiation across species, a process that is challenging to study in developing embryos from different species. While methods of human iPSCs to HSPCs are a work in progress, the existing iPSCs to HSPCs differentiation methods provide a platform for comparative studies across humans and their closely related species of nonhuman primates. In this study, we used iPSCs from human, chimpanzee and pigtailed macaque and differentiated them to HSPCs to explore how conserved iPSCs to HSPCs differentiation process across theses three species are. We observed differentiation of pig-tailed macaque and chimpanzee iPSCs in human differentiation media results in HSPCs with similar cell surface markers and gene expression profiles validated using flow cytometry and RNA-Seq. Our results indicate the pig-tailed macaque and chimpanzee iPSCs-derived HSPCs exhibit gene expression levels similar to those of humans with regards to several HSPCs marker genes including CD34+, CD90+, EPCR, and HLF. Functional validation of these iPSCs-derived HSPCs remains to be explored through in vivo transplantation. However, phenotypic analysis of HSPCs based on their gene expression profiles suggest that pig-tailed macaque iPSCs provide an appropriate model for studying humans iPSCs-derived HSPCs specifically for future studies. This is specially of high interest where functional validations (e.g., autologous transplantations) of human iPSCs-derived cells cannot be used.