Pig and human adult hematopoietic stem and progenitor cells are overall transcriptionally similar

Over the recent years, pigs have re-emerged as an alternative source of organs for xenotransplantation into humans with the promise to overcome a worldwide shortage of human donors. Xenotransplantation still faces critical issues with immune rejection that could be potentially solved by the generation of lymphohematopoietic chimeras. Moreover, pig hematopoietic stem and progenitor cells (HSPCs) can constitute an unlimited source of HSPCs for lifesaving HSPC transplantation in bone marrow (BM) failure and after chemotherapy, among other cell therapies. The generation of these hematopoietic chimeras requires a profound study of pig hematopoiesis including pig HSPCs. Importantly, through single-cell RNA sequencing of pig BM cells we identified pig HSPC populations transcriptionally similar to those in humans and many common transcriptional regulators of hematopoiesis evolutionarily preserved in erythromyeloid and lymphoid differentiation. This supports that hematopoiesis in pigs is hierarchically organized and regulated in a very similar fashion as in humans. We also provided a sorting strategy for the identification and isolation of several putative pig HSPC populations, which should open a new means to functionally study pig hematopoiesis.