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Thy-1 expression is linked to functional properties of primitive
hematopoietic progenitor cells from human umbilical cord blood
H Mayani and PM Lansdorp
Division of Hematology, Terry Fox Laboratory, British Columbia Cancer
Agency, Vancouver, Canada.
We have previously shown that the most primitive human hematopoietic cells
are included within a cell subpopulation expressing high levels of CD34 and
low or undetectable levels of CD45RA and CD71. In this study, cord blood
cells with this phenotype were sorted and further separated based on their
expression on the Thy-1 antigen. The proliferation and differentiation of
the purified cell fractions in response to a mixture of hematopoietic
cytokines was analyzed in serum- and stroma-free liquid cultures. Thy-1+
cells (25% of CD34+ CD45RAlo CD71lo cells) were particularly enriched for
high proliferative potential colony-forming cells (HPP-CFC; up to 45% of
the clonogenic cells), whereas Thy-1- cells were enriched for
multipotential colony- forming cells (CFU-MIX; up to 46% of the clonogenic
cells). When both subpopulations were cultured in serum-free liquid
cultures supplemented with a cytokine mixture that included steel factor,
interleukin-6 (IL- 6), granulocyte-macrophage colony-stimulating factor
(GM-CSF)/IL-3 fusion protein, M-CSF, G-CSF, and erythropoietin, Thy-1+
cells showed a much higher numerical expansion of CD34+ cells (30,000-fold)
and colony- forming cells (4,700-fold) than was observed in cultures
initiated with Thy-1- cells (900-fold increase in CD34+ cell numbers and
241-fold increase in CFC numbers). Cells coexpressing CD34 and Thy-1 were
only transiently expanded (up to 29-fold) and were not detected after day
22 of culture. When CD34+ CD45RAlo CD71lo Thy-1+ cells were cultured,
either in semi-solid or liquid cultures, in the presence of anti-Thy-1
antibody, a significant reduction in progenitor cell numbers (particularly
HPP-CFC) was observed. In contrast, CD34+ CD45RAlo CD71lo Thy-1- cells were
not affected by anti-Thy-1. The results of this study indicate that Thy-1
is expressed on primitive cord blood progenitors with the highest in vitro
proliferative potential, and further suggest that Thy-1 is involved in
hematopoietic cell development, possibly by mediating a negative signal
that results in inhibition of primitive cell proliferation.
Volume 83,
Issue 9,
pp. 2410-2417,
05/01/1994
Copyright © 1994 by The American Society of Hematology
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