The Haematopoietic Stem Cell Niche: New Insights into the Mechanisms Regulating Haematopoietic Stem Cell Behaviour

Abstract

The concept of the haematopoietic stem cell (HSC) niche was formulated by Schofield in the 1970s, as a region within the bone marrow containing functional cell types that can maintain HSC potency throughout life. Since then, ongoing research has identified numerous cell types and a plethora of signals that not only maintain HSCs, but also dictate their behaviour with respect to homeostatic requirements and exogenous stresses. It has been proposed that there are endosteal and vascular niches within the bone marrow, which are thought to regulate different HSC populations. However, recent data depicts a more complicated picture, with functional crosstalk between cells in these two regions. In this review, recent research into the endosteal/vascular cell types and signals regulating HSC behaviour are considered, together with the possibility of a single subcompartmentalised niche.

Extramedullary hematopoiesis: Elucidating the function of the hematopoietic stem cell niche (Review)

“…HSCs occur in the vicinity of, but not necessarily in direct contact with, osteoblastic bone-lining cells that constitute the endosteal niche regions. However, the sinusoidal endothelium also interacts with HSCs, and form the vascular niche (6 suggests that their effects may be more complicated due to functional crosstalk between cells within the two regions (8,9). Furthermore, the vascular niche has been suggested to regulate HSCs in a distinct mechanism or potentially harbor HSCs with various self-renewable properties (10)(11)(12).…”

Hematopoietic Stem Cell Niche: Role in Normal and Malignant Hematopoiesis

“…Activation of Notch receptors on HSCs has been shown to inhibit differentiation and enhance their self renewal capacity in vitro (Butler et al, 2011). Notch signalling is important in vivo for controlling HSC self renewal and differentiation during hematopoietic stress conditions (Lilly et al, 2011).…”

“…These cytokines are thought to be important as THPO and Ang-1 knockout mice have decreased numbers or defects in bone marrow HSCs. The interaction of Ang-1 with its Tie2 receptor activates β1-integrin and Ncadherin, enhances quiescence, and maintains the long term repopulating ability of HSCs; it also protects against apoptosis by activating the PI3K pathway (Lilly et al, 2011) • Osteopontin, a matrix glycoprotein expressed by the osteoblasts supports the adhesion of HSC to the osteoblastic niche and negatively regulates HSC proliferation, contributing to the maintenance of a quiescent state (Guerrouahen et al, 2011). …”

“…It was noted that whilst HSCs in the bone marrow drive hematopoiesis during the whole life of organisms, when they are removed from the bone marrow, they lose the ability to self-renewal, indicating similar dependence of HSCs on extrinsic signals (Lilly et al, 2011). The term 'niche' used for the specific HSC bone-marrow microenvironment was first coined by Schofield (1978), who observed that HSC growth was not supported in the spleen in the same manner as in the bone marrow; he also proposed that HSCs are in intimate contact with bone, and that cell-cell contact was responsible for the apparently unlimited proliferative capacity and inhibition of maturation of HSCs.…”

Expansion of human umbilical cord blood hematopoieticprogenitors with cord vein pericytes

“…The identification of cellular compartments of the HSC niche has recently been the subject of many studies (Bianco, 2011;Morrison et al, 2014). In bone marrow (BM), there is broad discussion of the possible presence of two niches able to maintain and regulate HSCs, which are the endosteal and vascular niches (Lilly et al, 2011). Previous reports suggested that N-cadherin + osteoblasts could be proposed to promote HSC quiescence through direct contact and secretion of some cytokines and extracellular matrix proteins (Bromberg et al, 2012;Greenbaum et al, 2012).…”