Distinct roles of Bcl-2 and Bcl-Xl in the apoptosis of human bone marrow mesenchymal stem cells during differentiation

Background

Adult mesenchymal stem cells (MSCs) can be maintained over extended periodsof time before activation and differentiation. Little is known about theprograms that sustain the survival of these cells.

Principal Findings

Undifferentiated adult human MSCs (hMSCs) did not undergo apoptosis inresponse to different cell death inducers. Conversely, the same inducers canreadily induce apoptosis when hMSCs are engaged in the early stages ofdifferentiation. The survival of undifferentiated cells is linked to theexpression of Bcl-Xl and Bcl-2 in completely opposite ways. Bcl-Xl isexpressed at similar levels in undifferentiated and differentiated hMSCswhile Bcl-2 is expressed only in differentiated cells. In undifferentiatedhMSCs, the down-regulation of Bcl-Xl is associated with an increasedsensitivity to apoptosis while the ectopic expression of Bcl-2 inducedapoptosis. This apoptosis is linked to the presence of cytoplasmic Nur 77 inundifferentiated hMSCs.

Significance

In hMSCs, the expression of Bcl-2 depends on cellular differentiation and canbe either pro- or anti-apoptotic. Bcl-Xl, on the other hand, exhibits ananti-apoptotic activity under all conditions.