The hematopoietic stem cell niche

Abstract

Hematopoietic stem cells (HSCs) possess the ability to self-renew and to differentiate to mature progeny along multiple different hematopoietic lineages. The function of HSCs depends upon the signals from surrounding cells found within the highly specialized microenvironment termed the hematopoietic stem cell niche. Understanding and exploiting the HSC niche is a goal of basic scientists and clinicians alike. Recent studies have focused on defining the cellular components and molecular factors critical to this microenvironment. Here we review recent findings, discuss unresolved questions, and examine the clinical implications of our current knowledge of the HSC niche.

Figure 1

In this model of the bone marrow microenvironment, the hematopoietic stem cell (HSC) receives a variety of signals from its niche. The signals are both positive (promote self-renewal) and negative (decrease self-renewal) on the HSCs. Osteoprogenitor cells (OPCs) provide a positive signal, while the more mature osteopontin (Opn)-expressing osteoblasts provide a negative signal. Mesenchymal stem cells (MSCs)/CXCL12-abundant reticular (CAR) cells and other pericytes associate tightly with the sinusoidal endothelial cells (SEC) of bone marrow blood vessels and interact with the HSC. Adipocytes form another compartment of the bone marrow and are felt to be negative regulators of the HSC.