Hematopoyesis

Hematopoiesis is the process by which different types of blood cells are produced from hematopoietic stem cells (HSCs). In adults, hematopoiesis occurs in the bone marrow, which is surrounded by reticular cells, stromal cells, and blood vessels. The process takes place in the spaces between these components, where HSCs continuously multiply and self-renew.

HSCs undergo asymmetric division to produce two daughter cells with different fates. One daughter cell self-renews like the parent cell, maintaining the HSC pool in the bone marrow. The other daughter cell differentiates into specialized cells such as myeloid progenitor cells and lymphoid progenitor cells in response to molecular factors released during tissue injury, growth spurts, or infection.

HSC progenitors can produce all types of blood cells due to their multipotent nature, including red blood cells, lymphocytes, macrophages, and natural killer cells. Once committed to their specific roles, these differentiated blood cells leave the bone marrow and enter blood vessels to migrate to their sites of action throughout the body.

Bone marrow contains two HSC populations with distinct characteristics. Dormant or quiescent HSCs are non-proliferative and remain attached to the inner bone surface. Active or primed HSCs rapidly proliferate in response to vascular endothelial growth factors and are located in the central marrow region, allowing them to respond quickly to physiological demands.

HSCs migrate from bone marrow into circulating blood by losing cell adherence molecules and chemokine receptor CXCR4. During HSC homing, they regain these molecules and receptors, allowing them to bind and anchor to target tissues following chemokine gradients. Homing to bone marrow is essential for regulating HSC homeostasis and maintaining the HSC pool through proliferation.

Hematopoiesis starts early during development on the seventh day of embryogenesis in a phase called the primitive wave. During this phase, the extraembryonic yolk sac produces erythroid cells and endothelial cells from a common precursor called hemangioblast. These erythroid cells provide oxygen to support the rapidly dividing embryo's growth.

During fetal development, hemangioblasts develop into hematopoietic stem cells that migrate to the liver. This represents a shift from the yolk sac as the primary hematopoietic site during the primitive wave to the liver during fetal stages, before hematopoiesis eventually becomes established in the bone marrow of adults.