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

Abstract

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.