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Transforming growth factor beta directly regulates primitive murine
hematopoietic cell proliferation
JR Keller, IK Mcniece, KT Sill, LR Ellingsworth, PJ Quesenberry, GK Sing and FW Ruscetti
Laboratory of Molecular Immunoregulation, Program Resources, Inc, National
Cancer Institute, Frederick, MD 21701.
We previously reported that transforming growth factor beta (TGF-beta)
selectively inhibits colony-stimulating factor-driven hematopoietic
progenitor cell growth. We report here that TGF-beta 1 can act directly on
hematopoietic progenitors to inhibit the growth of the most primitive
progenitors measurable in vitro. Highly enriched populations of
hematopoietic progenitor cells were obtained by isolating lineage negative
(Lin-), Thy-1-positive (Thy-1+) fresh bone marrow cells, or by isolating
cells from interleukin-3 (IL-3) supplemented bone marrow cultures
expressing Thy-1 antigen with the fluorescent activated cell sorter.
TGF-beta 1 inhibited IL-3-induced Thy-1 expression on Thy-1- negative
(Thy-1-) bone marrow cells in a dose-dependent manner with an ED50 of 5 to
10 pmol/L. In addition, TGF-beta 1 inhibited the formation of multipotent
and mixed colonies by isolated Thy-1+ cells, while single lineage
granulocyte and macrophage colonies were not affected. The growth of Thy-1+
Lin- cells incubated as single cells in Terasaki plates in medium
supplemented with IL-3 were inhibited by TGF-beta, demonstrating a direct
inhibitory effect. Hematopoietic stem cells, which have a high
proliferative potential (HPP) when responding to combinations of growth
factors in vitro, have been detected in the bone marrow of normal mice and
mice surviving a single injection of 5- fluorouracil. TGF-beta 1 inhibited
the growth of all subpopulations of HPP colony forming cells (CFC) in a
dose-dependent manner with an ED50 of 5 to 10 pmol/L. Thus, TGF-beta
directly inhibits the growth of the most immature hematopoietic cells
measurable in vitro.
Volume 75,
Issue 3,
pp. 596-602,
02/01/1990
Copyright © 1990 by The American Society of Hematology

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