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- Title
A Cross-Talk Between Stromal Cell-Derived Factor-1 and Transforming Growth Factor-β Controls the Quiescence/Cycling Switch of CD34<sup>+</sup> Progenitors Through FoxO3 and Mammalian Target of Rapamycin.
- Authors
Chabanon, Aurélie; Desterke, Christophe; Rodenburger, Emilie; Clay, Denis; Guerton, Bernadette; Boutin, Laetitia; Bennaceur-Griscelli, Annelise; Pierre-Louis, Olivier; Uzan, Georges; Abecassis, Lucile; Bourgeade, Marie-Françoise; Lataillade, Jean-Jacques; Le Bousse-Kerdilèsa, Marie-Caroline
- Abstract
biology. A balance between quiescence and proliferation of hematopoietic stem cells in interaction with the microenvironment is critical for sustaining long-term hematopoiesis and for protection against stress. We analyzed the molecular mechanisms by which stromal cell-derived factor-1 (SDF-1) exhibited a cell cycle-promoting effect and interacted with transforming growth factor-β (TGF-β), which has negative effects on cell cycle orchestration of human hematopoietic CD34+ progenitor cells. We demonstrated that a low concentration of SDF-1 modulated the expression of key cell cycle regulators such as cyclins, cyclin-dependent kinase inhibitors, and TGF-β target genes, confirming its cell cycle-promoting effect. We showed that a cross-talk between SDF-1- and TGF-β-related signaling pathways involving phosphatidylinositol 3-kinase (PI3K)/Akt phosphorylation participated in the control of CD34+ cell cycling. We demonstrated a pivotal role of two downstream effectors of the PI3K/Akt pathway, FoxO3a and mammalian target of rapamycin, as connectors in the SDF-1-/TGF-β-induced control of the cycling/quiescence switch and proposed a model integrating a dialogue between the two molecules in cell cycle progression. Our data shed new light on the signaling pathways involved in SDF-1 cell cycle-promoting activity and suggest that the balance between SDF-1- and TGF-β-activated pathways is critical for the regulation of hematopoietic progenitor cell cycle status.
- Subjects
CELL proliferation; CELL cycle; RAPAMYCIN; HEMATOPOIETIC stem cells; GROWTH factors; PHOSPHORYLATION; PROTEIN kinases
- Publication
Stem Cells, 2008, Vol 26, Issue 12, p3150
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1634/stemcells.2008-0219