1. Mesoblastic (Yolk Sac) Stage
The first stage of hemopoiesis begins around the 9th day of development and takes place in extraembryonic structures — primarily in the mesenchyme of the yolk sac wall. Specific "blood islands" form here. Cells located at the periphery of these islands flatten and form the endothelium of the primary vessels. The central cells round up, transforming into first-generation hematopoietic stem cells (HSCs).
A key feature of this stage is the intravascular formation of primary erythrocytes via a megaloblastic pathway. These precursors (megaloblasts) give rise to megalocytes — giant cells that often retain a nucleus and contain embryonic hemoglobin (Hb embryo).
Later, the character of the process evolves: erythropoiesis shifts to a normoblastic pathway, and the first leukocytes (exclusively granulocytes) appear extravascularly (outside the vessels). The accumulated 1st-generation HSCs migrate via the bloodstream to the liver.
2. Hepatic (Hepatosplenic) Stage
Starting from the 6th week of embryonic development, the center of hematopoiesis shifts to the liver bud. Unlike the yolk sac, the process here is extravascular — cells form around capillaries that grow into the liver lobules.
The liver produces a full spectrum of blood cells. Erythrocytes acquire normal dimensions (normocytes), and fetal hemoglobin (HbF) replaces the embryonic protein types.
It is the liver that generates second-generation stem cells, dispatching them to colonize the thymus, spleen, lymph nodes, and bone marrow. Hepatic hemopoiesis peaks at the 5th month, after which it gradually declines and stops completely by birth.
3. Medullary Stage and Organ Specialization
Stem cells migrating from the liver settle in the rudiments of new organs. Initially, all of them act universally, synthesizing all types of cells extravascularly. Adult hemoglobin (HbA) begins to appear in erythrocytes. However, in the postnatal period, their functions become strictly compartmentalized:
- Red Bone Marrow (RBM) (active from weeks 11–12). Becomes the central organ, producing all blood cells (except mature T lymphocytes and B-1 cells) and housing 3rd-generation HSCs.
- Thymus (from weeks 9–10). Rapidly reduces other lineages and transitions to a narrow specialization — antigen-independent maturation of T lymphocytes.
- Lymph nodes and spleen. Cease myelopoiesis (in lymph nodes by week 15, in the spleen up until birth). After lymphoid follicles form, they become organs of antigen-dependent maturation, where T and B lymphocytes migrate to encounter antigens.