Hematopoietic stem cells (HSC) are the preferred target population for ex vivo gene therapy with applications ranging from rare monogenetic diseases to HIV. Currently, HSCs are isolated by the marker CD34. However, use of this population has severe limitations. Fred Hutch researchers have identified a unique combination of genetic markers that defines a small subset within the CD34-expressing population, which represents HSCs with self-renewing capacity, multilineage potential, long-term engraftment capability and is conserved between human and nonhuman primate. This method to isolate, expand, and manipulate HSCs has dramatic potential to reduce the cost of goods for manufacturing of gene and cell based therapeutics and provides a quantitative measure of graft potency.