The intrinsic apoptosis caspase cascade regulates hematopoietic stem cell homeostasis and function

Abstract

Since the demonstration that overexpression of pro-survival Bcl-2 causes an expansion of hematopoietic stem cell (HSC) number (Domen et al. 2000 J Exp Med), it has become accepted that apoptotic death is a common fate for HSCs. Apoptosis is believed to be critical for regulating the size of the HSC pool. Consistent with this, mice lacking Caspase-3 were reported to have increased numbers of HSCs (Janzen et al. 2008 Cell Stem Cell). This, however, was ascribed to perturbations in cytokine signaling, rather than impaired HSC apoptosis.