How the niche regulates hematopoietic stem cells

Abstract

The hematopoietic stem cell (HSC) forms all types of blood cells of the hematopoietic system. In the adult, HSC are mainly quiescent, being mostly in G0/G1 phase of cell cycle during steady-state conditions. However, during hematopoietic stress, the stem cells respond quickly to regenerate the damaged hematopoietic system. To understand how environmental signals affect HSC and its progeny, it is essential to know the lineage relationships and transcriptional mechanisms controlling self-renewal, proliferation and differentiation. Because of the high possible output of blood cells from a single HSC, a tight regulation of these processes is extremely important. An essential component for this control is the marrow microenvironment, in this context also referred to as the HSC niche. The niche is heterogeneous and regulates stem cell metabolism through both surface-bound and soluble factors. Several signaling pathways have been shown to take part in these regulation processes, with Notch and especially Wnt signaling being the best studied ones. Dysregulation of the niche, for instance by environmental exposure, has recently been shown to lead to hematopoietic abnormalities. Thus, to understand the effect of the environment on hematopoiesis, it is of importance to study both HSC, its direct progeny and the cellular components of the niche. Detailed knowledge of the regulatory mechanisms operating between hematopoietic cells and their direct surroundings facilitates the study of how such signaling may be disrupted by environmental exposure.