p21cip1 mRNA is controlled by endogenous transforming growth factor-?1 in quiescent human hematopoietic stem/progenitor cells

Autor: Jacques Hatzfeld, Marie-Noëlle Monier, Karin Ducos, Antoinette Hatzfeld, Nicolas O. Fortunel, Béatrice Panterne
Rok vydání: 2000
Předmět:
Zdroj: Journal of Cellular Physiology. 184:80-85
ISSN: 1097-4652
0021-9541
DOI: 10.1002/(sici)1097-4652(200007)184:1<80::aid-jcp8>3.0.co;2-q
Popis: Transforming growth factor-β1 (TGF-β1) has been described as an efficient growth inhibitor that maintains the CD34+ hematopoietic progenitor cells in quiescence. The concept of high proliferative potential-quiescent cells or HPP-Q cells has been introduced as a working model to study the effect of TGF-β1 in maintaining the reversible quiescence of the more primitive hematopoietic stem cell compartment. HPP-Q cells are primitive quiescent stem/progenitor cells on which TGF-β1 has downmodulated the cytokine receptors. These cells can be released from quiescence by neutralization of autocrine or endogenous TGF-β1 with a TGF-β1 blocking antibody or a TGF-β1 antisense oligonucleotide. In nonhematopoietic systems, TGF-β1 cooperates with the cyclin-dependent kinase inhibitor, p21cip1, to induce cell cycle arrest. We therefore analyzed whether endogenous TGF-β1 controls the expression of the p21cip1 in the CD34+ undifferentiated cells using a sensitive in situ hybridization method. We observed that addition of anti-TGF-β1 is followed by a rapid decrease in the level of p21cip1 mRNA whereas TGF-β1 enhances p21cip1 mRNA expression concurrently with an inhibitory effect on progenitor cell proliferation. These results suggest the involvement of p21cip1 in the cell cycle control of early human hematopoietic quiescent stem/progenitors and not only in the differentiation of more mature myeloid cells as previously described. The modulation of p21cip1 observed in response to TGF-β1 allows us to further precise the working model of high proliferative potential-quiescent cells. J. Cell. Physiol. 184:80–85, 2000. © 2000 Wiley-Liss, Inc.
Databáze: OpenAIRE
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