Abstract
The bone marrow is a complex, finely regulated system that widely extends in the body. It has unique development, microstructure, and functional characteristics that adapt to the flocculating body needs in steady-state and stress conditions. The bone marrow is an essential tissue for investigating most hematologic disorders. The study of the pathobiology of human bone marrow facilitates understanding many of its observed changes in benign and malignant conditions. This chapter explains the bone marrow development from the embryo to early infancy and throughout life, emphasizing the critical function-regulating features and the role of different cellular and humoral elements. The discussion of the concept and functions of the hemopoietic niches focuses on the maturation of different hemopoietic lineages within the bone marrow.
TopIntroduction
The hematopoietic tissue is extended throughout the body and exhibits multiple functions, including its elements' proliferation, maturation, maintenance, senescence, and final destruction. It has a finite control regulated by lineage-specific factors and broadly-acting biological factors. In addition, the hemopoietic tissue is continuously communicated with other body systems through a finely adjusted homeostatic signaling network, allowing hemopoiesis to be sensitively responsive to fluctuating body needs.
The bone marrow is the final site of hemopoiesis from the late fetus through postnatal life and throughout life. It is structurally and functionally complex, exhibiting age and context-related adaptation.
This chapter will highlight the dynamics of the hemopoietic system focusing on the following main aspects:
- A.
The embryonic development of the hemopoietic tissue and its microenvironment.
- B.
An overview of bone marrow structure and Components
- C.
The main elements and functions of the bone marrow stroma
- D.
The development, differentiation, and regulations of different hemopoietic lineages
- E.
The concept of the hemopoietic niches and their differential functions
TopThe Ontogeny And Development Of The Hemopoietic System
The hemopoietic tissue appears as early as the first week of gestation from blood islands within the yolk sac. Then, it progresses through 4 main developmental and functional stages.
Key Terms in this Chapter
Gastrulation: A multilayered early embryonic structure developing from a single-layered hollow sphere of cells called a blastula.
Ikaros Gene: This is a zinc finger DNA-binding protein transcription factor gene, with crucial functions in the hematopoietic system and immune cell development and regulation, mainly in early B cells and CD4+ T cells. It also regulates the later stages of B cell development during VDJ recombination, expression of the B cell receptor, and T helper cells' differentiation and function.
miRNAs: A class of small non-coding RNAs of ~22nt in length involved in gene expression regulation at the posttranscriptional level by degrading their target mRNAs and inhibiting their translation.
Long-term Repopulating Stem Cell (LTR-HSC): A multipotential HSC with durable repopulation potential in functional transplantation assays. It is confined in the microenvironment in a quiescent non-motile state. It maintains blood cell production and host immunity throughout life and responds to changing body demands such as inflammation, injury, and blood loss.
Aorta-Gonad-Mesonephros (AGM): A region of embryonic mesoderm that develops from the para-aortic splanchnopleura area where the first definitive hematopoietic stem cells are created.
A Proliferation-Inducing Ligand (APRIL): A member of the tumor necrosis factor (TNF) superfamily with an essential role in maintaining humoral immune responses and survival of plasmablast in adult bone marrow.
Adventitial Reticular Cells (ARCs): Specialized pericytes of the bone marrow sinusoids arising from mesenchymal stem cells (MSCs) and constitute an essential element of the bone marrow stroma.