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Characterization of mouse lymphohematopoietic stem cells lacking spleen
colony-forming activity
RJ Jones, MI Collector, JP Barber, MS Vala, MJ Fackler, WS May, CA Griffin, AL Hawkins, BA Zehnbauer, J Hilton, OM Colvin and SJ Sharkis
Johns Hopkins Oncology Center, Johns Hopkins Medical Institutions,
Baltimore, MD 21287-8967, USA.
The classical definition of lymphohematopoietic stem cells (LHSC), the most
primitive progenitors of all blood cells, requires that they have the
capacity for self-renewal and for the long-term production of all blood
cell lineages. However, other characteristics of LHSC have been debated.
Our previous data suggested that mouse LHSC are very slowly proliferating
cells that generate delayed multilineage engraftment, while
"radioprotection" (rapid engraftment that will prevent early death from
radiation-induced marrow aplasia) results from more committed progenitors.
Alternatively, some groups have reported that mouse LHSC are responsible
for both radioprotection and long-term repopulation of all blood cell
lineages. A possible explanation for this difference is that cells with the
capacity for long-term production of all blood cell lineages are
biologically heterogeneous. We now show that 10 LHSC can generate all blood
cell lineages for the lifetime of the animal. However, these cells lacked
radioprotection and spleen colony-forming activity. LHSC were identified
and isolated by their small size, their lack of expression of antigens
characteristic of mature blood cell lineages, and their high expression of
aldehyde dehydrogenase. In addition, these cells were found to express
undetectable or low levels of many antigens presumed to mark LHSC,
including Thy-1, Ly-6A/E (Sca-1), c-kit, and CD34. There appears to be at
least two classes of LHSC with the capacity for long-term production of all
blood cell lineages: one that generates both radioprotection and long-term
engraftment and one that produces delayed but durable engraftment. Our data
suggest that this latter class may represent a very primitive class of
LHSC.
Volume 88,
Issue 2,
pp. 487-491,
07/15/1996
Copyright © 1996 by The American Society of Hematology
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