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a Laboratoire de Biologie des Cellules Souches Somatiques Humaines, Centre National de la Recherche Scientifique, Villejuif, France;
b Division Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Key Words. Hematopoiesis • Stem/progenitor cell • HPP-Q in vitro assay • Quiescence • TGF-ß receptor
Correspondence:
Jacques Hatzfeld, Ph.D., UPR 1983, 7, rue Guy Môquet, 94800 Villejuif, France. Telephone: 33-1-49-58-33-16; Fax: 33-1-49-58-33-15; e-mail: hatzfeld{at}infobiogen.fr
Genetic alterations of the signaling cascade of transforming growth factor-ß (TGF-ß) are often associated with neoplastic transformation of primitive cells. This demonstrates the key role for this pleiotropic factor in the control of quiescence and cell proliferation in vivo. In the high proliferative potential-quiescent cell (HPP-Q) in vitro assay, the use of TGF-ß1 blocking antibodies (anti-TGF-ß1) allows the detection within two to three weeks of primitive hematopoietic cells called HPP-Q, which otherwise would not grow. However, the possibility of triggering cell proliferation by blocking the cell-surface TGF-ß receptors has not been investigated until now. We have tested here the efficiency of a blocking antibody against TGF-ßRII (anti-TGF-ßRII) on CD34+CD38– hematopoietic cells, a subpopulation enriched in primitive stem/progenitor cells, and compared its effect with that of anti-TGF-ß1. About twice as many HPP colony-forming cells were detected in the presence of anti-TGF-ß1 or anti-TGF-ßRII, compared to the control (p < 0.02). Moreover, anti-TGF-ßRII was as efficient as anti-TGF-ß1 for activating multipotent HPP-granulocyte erythroid macrophage megakaryocyte and HPP-Mix, bipotent HPP-granulocyte-macrophage (GM) and unipotent HPP-G, HPP-M and HPP-BFU-E. We therefore propose the use of anti-TGF-ßRII to release primitive cells from quiescence in the HPP-Q assay. This strategy could be extended to nonhematopoietic tissues, as TGF-ß1 may be a pleiotropic regulator of somatic stem cell quiescence.
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