Hierarchy of Hematopoiesis: The 6 Classes
The entire process of postembryonic hematopoiesis represents a strict hierarchy where cells gradually lose their universality while acquiring specific traits. There are six sequential classes:
- Class I. Stem Cells. Pluripotent (can become any blood cell). They divide rarely and are capable of self-renewal via asymmetric division.
- Class II. Progenitor Cells (Hemopoietic Progenitors). Multi- or oligopotent. They are already committed, meaning their developmental choice is restricted (e.g., myelopoiesis or lymphopoiesis precursors). Their self-renewal potential is reduced.
- Class III. Unipotent Cells. Strictly programmed to differentiate into only one specific type of formed element (with the exception of the erythroid lineage, which has two stages).
- Class IV. Blasts. These are the first cells that can be distinguished from one another under a microscope due to the onset of specific syntheses (they become larger and lighter). The capacity for colony formation is lost.
- Class V. Maturing Cells. They undergo a cascade of morphological changes. Each stage can be clearly identified.
- Class VI. Mature Cells. The final formed elements (erythrocytes, platelets, leukocytes) that enter the bloodstream.
Characteristics of Early Precursors (Classes I–III)
Cells of the first three classes are visually indistinguishable from one another—under the microscope, they look like small lymphocytes. Differentiation at these stages occurs covertly at the genome level.
They possess a unique capability—the phenomenon of colony formation. When a single such cell divides, it can form an entire clonal colony (hence the name colony-forming units, or CFUs). The phenomenon of repopulation is also characteristic of them: they can enter the bloodstream, circulate, and resettle in hematopoietic organs.
Regulation and Types of Hematopoiesis
Cell differentiation is controlled by specific factors. For instance, Class II cells become sensitive to humoral regulators (poietins): erythropoietin stimulates the erythrocytic lineage, and thrombopoietin stimulates the megakaryocytic lineage.
Depending on the ratio of cells in the bone marrow, two types of hematopoiesis are distinguished:
- Homoblastic (normal): the pool of early precursors is small, and the absolute majority consists of dividing Class V cells (maturing cells).
- Heteroblastic (in pathology, e.g., acute blood loss): the proportion of mature and maturing forms decreases due to their active release into the bloodstream, while the proportion of early forms increases compensatorily.
Experimental Evidence
The ability of early cells to form colonies was proven using the radiation chimera method ( spleen colony assay).
Essence of the experiment:
- Recipient mice are irradiated with a lethal dose, completely destroying their native bone marrow.
- Bone marrow cells from a healthy donor mouse are injected.
- After some time, nodular colonies appear on the recipient's spleen.
Each such nodule is a clone derived from a single transplanted Class I, II, or III cell.