Hematopoietic stem cells (HSCs) give rise to all of the cells of the blood, including those of the immune system. The abundance of these cells is determined not only by proliferation but also by whether the developing cells undergo apoptosis, programmed cell death. Opferman et al. show that MCL-1 is a critical regulator of this cell death decision in HSCs. MCL-1 is an antiapoptotic factor that prevents activation of the apoptosis-inducing proteins BAX and BAK. Conditional deletion of the MCL-1 gene in mice caused loss of HSCs. When cells lacking MCL-1 were isolated from conditional knockout animals and cultured in vitro, MCL-1 was required to allow stem cell factor to promote survival of bone marrow cell progenitors.
J. T. Opferman, H. Iwasaki, C. C. Ong, H. Suh, S.-I. Mizuno, K. Akashi, S. J. Korsmeyer, Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. Science 307, 1101-1104 (2005). [Abstract] [Full Text]