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 CD34neg-SCID repopulating cells, or CD34neg-SRC. CD34neg-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 CD34neg-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.
Bhatia
M
M
Research Institute, Hospital for Sick Children, Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada.
Bonnet
D
D
Murdoch
B
B
Gan
O I
OI
Dick
J E
JE
D000818:Animals; D018952:Antigens, CD34; D018929:Cell Culture Techniques; D002469:Cell Separation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000502:physiology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D010641:Phenotype
D018952:Antigens, CD34