1. Mesoblastic (yolk sac) stage
The first stage of hematopoiesis starts from the 9th day of development and takes place in extraembryonic structures—primarily in the mesenchyme of the yolk sac wall. Specific "blood islands" are established here. Cells located at the periphery of such an island flatten and form the endothelium of the primary vessels. The central cells round up, turning into 1st-generation hematopoietic stem cells (HSCs).
A key feature of this stage is intravascular formation of primary erythrocytes via the megaloblastic type. Precursors (megaloblasts) give rise to megalocytes—giant cells that often retain a nucleus and contain embryonic hemoglobin (Hb embryo).
Later, the nature of the process evolves: erythropoiesis changes to normoblastic, and outside the vessels (extravascularly), the first leukocytes appear, represented exclusively by granulocytes. The accumulated 1st-generation HSCs migrate with the bloodstream into the liver.
2. Hepatic (hepatosplenic) stage
Starting from the 6th week of embryonic development, the center of hematopoiesis shifts to the liver rudiment. Unlike the yolk sac, the process here proceeds extravascularly—cells are formed around capillaries that grow into the liver lobules.
A full spectrum of blood formed elements is formed in the liver. Erythrocytes acquire normal dimensions (normocytes), and embryonic protein types are replaced by fetal hemoglobin (HbF).
It is the liver that generates 2nd-generation stem cells, sending them out to colonize the thymus, spleen, lymph nodes, and bone marrow. The activity of hepatic hemopoiesis reaches its peak in the 5th month, after which it begins to gradually fade and stops completely by the time of birth.
3. Medullary stage and organ specialization
Stem cells migrated from the liver settle in the rudiments of new organs. Initially, they all act universally, synthesizing any types of cells extravascularly. Adult hemoglobin (HbA) begins to appear in erythrocytes. However, in the postnatal period, their functions are strictly separated:
- Red bone marrow (RBM) (active from the 11th–12th week). It becomes the central organ, producing all blood cells (except mature T-lymphocytes and B1-cells) and storing 3rd-generation HSCs.
- Thymus (from the 9th–10th week). It rapidly reduces other lineages and transitions to a narrow specialization—antigen-independent maturation of T-lymphocytes.
- Lymph nodes and spleen. They cease myelopoiesis (in lymph nodes—until the 15th week, in the spleen—up to birth). After the formation of lymphoid follicles, they become organs of antigen-dependent maturation, where T- and B-lymphocytes are directed for contact with an antigen.
Briefly: answers to topical questions
What stages of erythropoiesis (erythrocyte maturation) are distinguished in the red bone marrow?
The sequence of cell differentiation during erythropoiesis includes several stages. The following phases are distinguished during maturation:
- Burst-forming unit (BFU-E) — an early stage of unipotent cells capable of explosive division.
- Unipotent progenitor (CFU-E) — a more differentiated cell.
- Proerythroblast — a class IV cell retaining the ability to undergo mitosis.
- Basophilic erythroblast — a stage with intensive accumulation of ribosomes.
- Polychromatophilic erythroblast — a stage of systematic change in tinctorial properties.
- Oxyphilic erythroblast (normoblast) — the stage preceding the loss of the nucleus.
- Reticulocyte — an anucleate cell form.
- Mature erythrocyte — the final stage of development, characterized by the accumulation of hemoglobin and reduction of organelles.
What surface clusters of differentiation (CD markers) are characteristic of the hematopoietic stem cell?
The key immunological marker of hematopoietic stem cells is the CD34 antigen. This marker is expressed on the most primitive stem cells as well as on their differentiated precursors. As the cell develops, its presence changes: on mature hematopoietic cells, CD34 expression is completely absent. Determining the total pool of cells with this marker is of paramount clinical importance, since the timing of hematopoietic recovery after transplantation depends precisely on their number.
To avoid confusing early hematopoiesis terms: "MESOblastic" is the name of the STAGE (from localization in the yolk sac mesenchyme), while "MEGALOblastic" is the TYPE of cells (huge megalocytes).
Class and exam questions
Where and how are primary erythrocytes formed?
They originate in the mesenchyme of the yolk sac wall strictly inside primary blood vessels (intravascularly) via the megaloblastic pathway.
What is the difference between hematopoiesis in the liver and in the yolk sac?
In the liver, the process proceeds extravascularly, all types of blood cells are formed, and erythrocytes have normal sizes (normocytes) and contain fetal hemoglobin (HbF).
Which blood cells are not synthesized in the adult red bone marrow?
The red bone marrow produces all formed elements, with the exception of mature T-lymphocytes (they mature in the thymus) and B1-cells.
What else to study on this topic
- Morphological differences of the proerythroblast (class IV) and causes of its basophilia
- Classes of progenitor cells: types of class III unipotent cells (BFU-E and CFU-E)
- Tinctorial properties of erythroblasts (class V) and the systematic change in cytoplasm coloration
- Mechanism of vasculogenesis in the "blood islands" of the yolk sac
- Difference between antigen-independent and antigen-dependent lymphocyte maturation
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