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Differentiation

Transforming growth factor-β1 transcriptionally activates CD34 and prevents induced differentiation of TF-1 cells in the absence of any cell-cycle effects

Leukemia volume 16, pages 94–105 (2002)Cite this article

Abstract

A number of cytokines modulate self-renewal and differentiation of hematopoietic elements. Among these is transforming growth factor β1 (TGF-β1), which regulates cell cycle and differentiation of hematopoietic cells, but has pleiotropic activities depending on the state of responsiveness of the target cells. It has been previously shown by us and other authors that TGF-β1 maintains human CD34+ hematopoietic progenitors in an undifferentiated state, independently of any cell cycle effects, and that depletion of TGF-β1 triggers differentiation accompanied by a decrease in CD34 antigen expression. In the present work, we show that exogenous TGF-β1 upregulates the human CD34 antigen in the CD34+ cell lines TF-1 and KG-1a, but not in the more differentiated CD34− cell lines HL-60 and K-562. We further studied this effect in the pluripotent erythroleukemia cell line TF-1. Here, TGF-β1 did not effect cell growth, but induced transcriptional activation of full-length CD34 and prevented differentiation induced by differentiating agents. This effect was associated with nuclear translocation of Smad-2, activation of TAK-1, and with a dramatic decrease in p38 phosphorylation. In other systems TGF-β1 has been shown to activate a TGF-β-activated kinase 1 (TAK1), which in turn, activates p38. The specific inhibitor of p38 phosphorylation, SB202190, also increased CD34 RNA expression, indicating the existence of a link between p-38 inhibition by TGF-β1 and CD34 overexpression. Our data demonstrate that TGF-β1 transcriptionally activates CD34 and prevents differentiation of TF-1 cells by acting independently through the Smad, TAK1 and p38 pathways, and thus provide important clues for the understanding of hematopoietic development and a potential tool to modify response of hematopoietic cells to mitogens or differentiating agents.

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Authors and Affiliations

  1. Dept of Gynecology, Catholic University, Rome, Italy

    M Marone, G Scambia, G Bonanno & D de Ritis

  2. Dept of Hematology, Catholic University, Rome, Italy

    S Rutella, G Leone & L Pierelli

  3. Laboratorio di Immunologia, AMB-PRO-TOSS, ENEA CR, Casaccia, Rome, Italy

    F Guidi

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Marone, M., Scambia, G., Bonanno, G. et al. Transforming growth factor-β1 transcriptionally activates CD34 and prevents induced differentiation of TF-1 cells in the absence of any cell-cycle effects. Leukemia 16, 94–105 (2002). https://doi.org/10.1038/sj.leu.2402334

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