Hematopoietic Stem Cell and Its Bone Marrow Niche

Abstract

Stem cells do not thrive without their niche. The bone marrow microenvironment is where hematopoietic stem cells maintain their cell state while receiving physiological input to modify their activity in response to changing physiological demands. The complexity of the bone marrow microenvironment is being unraveled and indicates that multiple different cell types contribute to the regulation of stem and progenitor cells. Further, it is becoming evident that the bone marrow represents a composite of niches with different components and different functional roles in hematopoiesis. It is now evident that alterations in specific stromal cells that comprise the bone marrow microenvironment can contribute to hematologic pathology. In this chapter, we will review the history of the niche concept, evolving information about its components and how niche dysfunction may contribute to disease.

Keywords: Bone marrow; Cytokine; Engraftment; Extracellular matrix protein; Hematopoietic stem cell; Mesenchymal stem cell; Microenvironment; Mobilization; Niche; Osteolineage cells; Perivascular cell; Reconstitution; Stroma; Transgenic mouse model; Transplantation.

Fig. 1

The hypothetical view of the stem cell niche from R. Schofield. The stem cell can become the daughter cell, CFU-S, once the stem cell leaves its niche. But if the stem cell finds and reoccupies the niche, it will itself return to its stem cell state. Adopted from Schofield, R. (1978). The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells, 4, 7–25.

Fig. 2

The hematopoietic stem cell niche. Extrinsic signals including growth factors, cytokines, morphogens, extracellular matrix proteins, and adhesion molecules regulate the behavior of hematopoietic stem cells (HSCs) and protect them from exhaustion, although few have been pinpointed to derive from a specific cell source. Recent advances in flow cytometry, transgenic mouse models, and intravital microscopy have revolutionized our understanding of the BM niche and how it controls various stem cell behaviors including self-renewal, proliferation, differentiation, lineage commitment, and mobilization. Enlisted in the diagram are cellular and molecular participants that have been experimentally shown to impact different HSC activities through promoter-specific Cre deletion or overexpression. But the diagram is far from complete and represents an active area of ongoing investigation.