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Two forms of transforming growth factor-β distinguished by multipotential haematopoietic progenitor cells

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Abstract

Type-β transforming growth factors (TGF-βs) are polypeptides that act hormonally to control proliferation and differentiation of many cell types1,2. Two distinct homodimeric TGF-β polypeptides, TGF-β1 and TGF-β2 have been identified which show ˜70% amino-acid sequence similarity3,4. Despite their structural differences, TGF-β1 and TGF-β2 are equally potent at inhibiting epithelial cell proliferation and adipogenic differentiation3. The recent immunohistochemical localization of high levels of TGF-β in the bone marrow and haematopoietic progenitors of the fetal liver5 has raised the possibility that TGF-βs might be involved in the regulation of haematopoiesis. Here we show that TGF-β1, but not TGF-β2, is a potent inhibitor of haematopoietic progenitor cell proliferation. TGF-β1 inhibited colony formation by murine factor-dependent haematopoietic progenitor cells in response to interleukin-3 (IL-3) or granulocyte-macrophage colony stimulating factor (GM-CSF), as well as colony formation by marrow progenitor cells responding to CSF-1 (M-CSF). The progenitor cell lines examined were ˜100-fold more sensitive to TGF-β1 than TGF-β2, and displayed type-I TGF-β receptors with affinity ˜20-fold higher for TGF-β1 than TGF-β2. These results identify TGF-β1 as a novel regulator of haematopoiesis that acts through type-I TGF-β receptors to modulate proliferation of progenitor cells in response to haematopoietic growth factors.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, Massachusetts, 01605, USA

    Masatsugu Ohta, Joel S. Greenberger & Pervin Anklesaria

  2. Department of Biochemistry, University of Massachusetts Medical School, Worcester, Massachusetts, 01605, USA

    Anna Bassols & Joan Massagué

Authors
  1. Masatsugu Ohta
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  2. Joel S. Greenberger
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  3. Pervin Anklesaria
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  4. Anna Bassols
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  5. Joan Massagué
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Ohta, M., Greenberger, J., Anklesaria, P. et al. Two forms of transforming growth factor-β distinguished by multipotential haematopoietic progenitor cells. Nature 329, 539–541 (1987). https://doi.org/10.1038/329539a0

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  • DOI: https://doi.org/10.1038/329539a0

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