Niche heterogeneity in the bone marrow

Abstract

In adult mammals, hematopoietic stem cells (HSCs) are defined by their abilities to self-renew and to differentiate to form all blood cell lineages. These rare multipotent cells occupy specific locations in the bone marrow (BM) microenvironment. The specific microenvironment regulating HSCs, commonly referred to as the niche, comprises multiple cell types whose exact contributions are under active investigation. Understanding cellular cross talk involving HSCs in the BM microenvironment is of fundamental importance for harnessing therapies against benign and malignant blood diseases. In this review, we summarize and evaluate recent advances in our understanding of niche heterogeneity and its influence on HSC function.

Keywords: BM; microenvironment; niche; stem cells.

Figure 1

Diagram illustrating the quiescent arteriolar and the active sinusoidal HSC niches during BM homeostasis. The BM microenvironment hosts various hematopoietic and non-hematopoietic cell types, including macrophages, megakaryocytes, lymphocytes, neutrophils, pericytes, and endothelial and Schwann cells. These cells contribute to the BM microenvironment and regulate HSCs directly by secretion of cytokines such as CXCL12 and SCF and/or indirectly through signaling via other cells, for example, by prostaglandin E2, which increases the expression of CXCL12 in perivascular cells. Deeply quiescent (dormant) HSCs are found around arterioles, while activated HSCs, which are significantly more abundant than dormant HSCs, are located near sinusoids. TGFβ, transforming growth factor β; THPO, thrombopoietin; PTN, pleiotrophin; PGE2, prostaglandin E2; EGF, epidermal growth factor; T_reg, CD4⁺CD25⁺FOXP3⁺ regulatory T cell.