Stress-induced haematopoietic stem cell proliferation: new roles for p38α and purine metabolism

Haematopoietic stem cells (HSCs) are self-renewing cells that sustain the production of all blood and immune cell lineages throughout life by residing at the top of the haematopoietic hierarchy. They first arise early in embryogenesis and their site of action changes during development. In adult mammals, HSCs reside in the bone marrow within a complex microenvironment termed the HSC niche (1). They are defined by their ability to completely repopulate the entire blood system of a recipient, resulting in the formation of red blood cells, megakaryocytes, myeloid cells and lymphocytes, and in order to do this they are able to undergo asymmetric division where one daughter cell remains as a HSC whilst the other becomes committed to differentiation (2). In the bone marrow, to prevent exhaustion and to preserve their ability to self-renew, HSCs are normally maintained in a dormant or quiescent state, from which they can be rapidly awakened in response to haematological stress (3). How this is regulated is an important issue and in a recent issue of Cell Stem Cell, Karigane et al. have shed new light on how the p38 MAPK pathway promotes stress-induced proliferation in HSCs (4).