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Transforming growth factor beta 1 directly and reversibly inhibits the
initial cell divisions of long-term repopulating hematopoietic stem cells
E Sitnicka, FW Ruscetti, GV Priestley, NS Wolf and SH Bartelmez
Department of Pathology, Medical School, University of Washington, Seattle,
USA.
Hematopoiesis appears to be regulated, in part, by a balance between
extracellular positive and negative growth signals. Transforming growth
factor beta-1 (TGF-beta 1) has been shown to be a negative regulator of
primitive hematopoietic cells. This study examined the direct effect of
TGF-beta 1 on the proliferation and differentiation of long-term
repopulating hematopoietic stem cells (LTR-HSC) in vitro. We previously
reported a cell fractionation approach that includes the selection of low
Hoescht 33342/low Rhodamine 123 (low Ho/Rh) cell fractions that are highly
enriched for long-term repopulating cells (LTR-HSC) and also clone to a
very high efficiency in the presence of stem cell factor (SCF) +
interleukin-3 (IL-3) + IL-6: 90% to 100% of individually cultured low Ho/Rh
cells formed high proliferative potential clones. This high cloning
efficiency of an LTR-HSC enriched cell population enabled proliferation
inhibition studies to be more easily interpreted. In this report, we show
that the continuous presence of TGF-beta 1 directly inhibits the cell
division of essentially all low Ho/Rh cells (in a dose-dependent manner)
during their 0 to 5th cell division in vitro. Therefore, it follows that
TGF-beta 1 must directly inhibit the proliferation of LTR-HSC contained
within these low Ho/Rh cells. The time required for some low Ho/Rh cells to
undergo their first cell division in vitro was also prolonged in the
presence of TGF-beta 1. Furthermore, when low Ho/Rh cells were exposed to
TFG-beta 1 for varying lengths of time before neutralization of the
TGF-beta 1 by monoclonal antibody, the ability to form macroclones was
markedly decreased after approximately 4 days of TGF-beta 1 exposure. In
addition, 1 to 10 ng/mL of TGF-beta 1 resulted in a maintenance of high
proliferative potential-colony-forming cell (HPP-CFC) during 8 days of
culture compared with loss of HPP-CFC in cultures with no added TGF- beta
1. In conclusion, this study shows that TGF-beta 1 directly inhibits the
initial stages of proliferation of LTR-HSC and appears to slow the
differentiation of daughter cells of low Ho/Rh cells.
Volume 88,
Issue 1,
pp. 82-88,
07/01/1996
Copyright © 1996 by The American Society of Hematology
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|
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[Full Text]
[PDF]
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|
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