A newly discovered class of human hematopoietic cells with SCID-repopulating
activity
Mickie Bhatia1, 2, Dominique Bonnet1, 3, Barbara Murdoch1, Olga I. Gan1
& John E. Dick1
1
Programs in Cancer/Blood and Developmental Biology,
Research Institute, Hospital for Sick Children, 555 University
Avenue, Toronto, Ontario, Canada,
M5G 1X8 and Department of Molecular and Medical Genetics, University
of Toronto
2
present address: The John. P. Robarts Research Institute,
Gene Therapy and Molecular Virology, 100 Perth Drive,
London, Ontario, N6A 5K8 and Department of
Mircobiology and Immunology, University of Western Ontario
3
present address: Coriell Institute for Medical Research
, 401 Haddon Avenue, 08103 Camden,
New Jersey M.B and D.B. contributed equally to this work
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.
