Distinct Roles of Bcl-2 and Bcl-Xl in the Apoptosis of Human Bone Marrow Mesenchymal Stem Cells during Differentiation

Lisa Oliver (1, 2) , Erika Hue (1, 2) , Julien Rossignol (3, 2) , Gwenola Bougras (1, 2) , Philippe Hulin (4, 2) , Philippe Naveilhan (3, 2) , Dominique Heymann (2) , Laurent Lescaudron (3, 2) , François M Vallette (1, 2)

1 CRCINA-ÉQUIPE 9 - Apoptosis and Tumor Progression
2 UFR MEDECINE - Université de Nantes - UFR de Médecine et des Techniques Médicales
3 INSERM UMR 643
4 Plateforme MicroPicell [Nantes]

Background: Adult mesenchymal stem cells (MSCs) can be maintained over extended periods of time before activation and differentiation. Little is known about the programs that sustain the survival of these cells. Principal Findings: Undifferentiated adult human MSCs (hMSCs) did not undergo apoptosis in response to different cell death inducers. Conversely, the same inducers can readily induce apoptosis when hMSCs are engaged in the early stages of differentiation. The survival of undifferentiated cells is linked to the expression of Bcl-Xl and Bcl-2 in completely opposite ways. Bcl-Xl is expressed at similar levels in undifferentiated and differentiated hMSCs while Bcl-2 is expressed only in differentiated cells. In undifferentiated hMSCs, the down-regulation of Bcl-Xl is associated with an increased sensitivity to apoptosis while the ectopic expression of Bcl-2 induced apoptosis. This apoptosis is linked to the presence of cytoplasmic Nur 77 in undifferentiated hMSCs. Significance: In hMSCs, the expression of Bcl-2 depends on cellular differentiation and can be either pro- or anti-apoptotic. Bcl-Xl, on the other hand, exhibits an anti-apoptotic activity under all conditions.

Domains: Life Sciences [q-bio]; Cancer

Lisa Oliver, Erika Hue, Julien Rossignol, Gwenola Bougras, Philippe Hulin, et al.. Distinct Roles of Bcl-2 and Bcl-Xl in the Apoptosis of Human Bone Marrow Mesenchymal Stem Cells during Differentiation. PLoS ONE, 2011, 6 (5), pp.e19820. ⟨10.1371/journal.pone.0019820⟩. ⟨hal-01968410⟩