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

• Published in: Nature (London) 1987-10, Vol.329 (6139), p.539-541
• Main Authors: Ohta, Masatsugu, Greenberger, Joel S, Anklesaria, Pervin, Bassols, Anna, Massagué, Joan
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell Division - drug effects; Cell physiology; Colony-Stimulating Factors - antagonists & inhibitors; Erythropoietin - antagonists & inhibitors; Fundamental and applied biological sciences. Psychology; Hematopoiesis - drug effects; Humanities and Social Sciences; Interleukin-3 - antagonists & inhibitors; letter; Molecular and cellular biology; multidisciplinary; Peptides - pharmacology; Receptors, Cell Surface - physiology; Receptors, Transforming Growth Factor beta; Science; Science (multidisciplinary); Transforming Growth Factors
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/329539a0

Type-β transforming growth factors (TGF-βs) are polypeptides that act hormonally to control proliferation and differentiation of many cell types 1,2 . Two distinct homodimeric TGF-β polypeptides, TGF-β1 and TGF-β2 have been identified which show ˜70% amino-acid sequence similarity 3,4 . Despite their structural differences, TGF-β1 and TGF-β2 are equally potent at inhibiting epithelial cell proliferation and adipogenic differentiation 3 . The recent immunohistochemical localization of high levels of TGF-β in the bone marrow and haematopoietic progenitors of the fetal liver 5 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.