A newly discovered class of human hematopoietic cells with SCID-repopulating activity

The detection of primitive hematopoietic cells based on repopulation of immune-deficient mice is a powerful tool to characterize the human stem-cell compartment. Here, we identify a newly discovered human repopulating cell, distinct from previously identified repopulating cells, that initiates multilineage hematopoiesis in NOD/SCID mice. We call such cells CD34(neg)-SCID repopulating cells, or CD34(neg)-SRC. CD34(neg)-SRC are restricted to a Lin(-)CD34(-)CD38(-) population without detectable surface markers for multiple lineages and CD38 or those previously associated with stem cells (HLA-DR, Thy-1 and CD34). In contrast to CD34(+) subfractions, Lin(-)CD34(-)CD38(-) cells have low clonogenicity in short-and long-term in vitro assays. The number of CD34(neg)-SRC increased in short-term suspension cultures in conditions that did not maintain SRC derived from CD34(+) populations, providing independent biological evidence of their distinctiveness. The identification of this newly discovered cell demonstrates complexity of the organization of the human stem-cell compartment and has important implications for clinical applications involving stem-cell transplantation.