Scientists have finally tracked down the precise subset of blood-forming (also known as hematopoietic) stem cells, or HSCs, that are capable of fully repopulating the bone marrow after transplantation in nonhuman primates. Their findings promise to make future efforts for stem cell transplants, gene therapy, and genome editing more efficient. The gold standard target for HSC transplantation is cells that bear the surface marker CD34. In their new study, Radtke and colleagues followed hundreds of thousands of cells immediately after transplant and subsequently over the course of 7.5 years. Contrary to previous reports that successive waves of progenitor cells expand and contract to establish the new donor bone marrow, Radtke et al. focused in on a distinct group of CD34+ HSCs that took hold early after transplantation and went on to produce all cell lineages that constitute a complete blood system. That potent population could be distinguished by the presence or absence of three cell surface markers - CD34+ CD45RA- CD90+ - and the researchers determined the minimum numbers of such cells that were necessary in primate models for successful bone marrow transplantation (defined as sustained neutrophil and platelet recovery). Importantly, Radtke et al. demonstrated similar gene expression profiles between primate and human CD34+ CD45RA- CD90+ cells, hinting at potential implications for human transplantation and other types of gene therapy studies.