Hemopoiesis hierarchy: 6 classes
The entire process of postembryonic hemopoiesis represents a strict hierarchy where cells gradually lose their universality while acquiring specific features. There are six consecutive classes:
- Class I. Stem cells. Pluripotent (can become any blood cell). Divide rarely, capable of self-maintenance through asymmetric division.
- Class II. Hemistem cells. Multi- or oligopotent. Already committed, meaning their choice is restricted (e.g., precursors of myelopoiesis or lymphopoiesis). Self-maintenance potential is reduced.
- Class III. Unipotent cells. Strictly programmed to transform into only one type of form element (the exception is 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, lighter). Colony-forming ability is lost.
- Class V. Maturing cells. Undergo a cascade of morphological changes. Each stage can be clearly identified.
- Class VI. Mature cells. Terminal form elements (erythrocytes, platelets, leukocytes) entering the bloodstream.
Characteristics of early precursors (Classes I–III)
Cells of the first three classes are visually indistinguishable from each other—under the microscope, they look like small lymphocytes. Differentiation at these stages occurs covertly, at the genome level.
They possess a unique ability—the colony-forming phenomenon. Upon division, a single such cell can form an entire clone colony (hence the name—colony-forming units, or CFU). They are also characterized by the repopulation phenomenon: they can enter the bloodstream, circulate in it, and settle back into hemopoietic organs.
Regulation and types of hemopoiesis
Cell differentiation is controlled by specific factors. For instance, Class II cells become sensitive to humoral regulators (poietins): erythropoietin stimulates the erythrocytic lineage, while thrombopoietin stimulates the megakaryocytic lineage.
Depending on the ratio of cells in the bone marrow, two types of hemopoiesis are distinguished:
- Homoblastic (normal): the pool of early precursors is small, with the absolute majority consisting of dividing Class V cells (maturing).
- Heteroblastic (in pathology, e.g., 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 has been proven using the radiation chimera method (spleen colony assay).
Essence of the experiment:
- Recipient mice are irradiated with a lethal dose, completely destroying their own 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 arising from a single transplanted Class I, II, or III cell.
Briefly: answers to topical questions
Which humoral factors and interleukins regulate blood cell differentiation?
Differentiation and activity of hemopoietic cells are regulated by hemopoietins; the regulation of hemopoiesis also includes inhibitors. Stimulating humoral factors include:
- Colony-stimulating factors (CSFs): Multi-CSF, erythropoietin (E-CSF), thrombopoietin, granulocyte CSF (G-CSF), thymopoietins. Their target is predominantly cells of early hemopoiesis stages; their function is determining the direction of differentiation.
- At the stage of myeloid precursors, differentiation is influenced by leukopoietin, erythropoietin, thrombopoietin; for Class II cells, regulators determine further development: erythropoietin → CFU-GEMM (erythroid), leukopoietin → CFU-GM, thrombopoietin → CFU-Meg.
- Interleukins (IL-1–IL-7): act on relatively differentiated cells, regulating their activity and proliferation capacity; IL-3 is required at all stages of all hemopoiesis lineages.
Hemopoiesis inhibitors include chalones (negative feedback from mature cells), as well as prostaglandins, interferon, and glucocorticoids.
What specific stages of morphological changes (Class V) does a cell undergo during erythropoiesis?
During erythropoiesis, a maturing Class V cell passes through a chain of sequentially transitioning stages. These include:
- Basophilic erythroblast — the stage at which ineffective erythropoiesis with the death of some cells may occur.
- Polychromatophilic erythroblast — an intermediate stage of maturation in the erythroid lineage.
- Orthochromatic erythroblast — the stage from which reticulocytes are formed after the loss of the nucleus.
What six differentiation directions does myelopoiesis include?
Myelopoiesis includes six directions of blood form element differentiation. These include:
- Erythrocytes — products of erythroid lineage differentiation.
- Monocytes — cells of the agranulocytic lineage.
- Platelets — blood platelets of the thrombocytic lineage.
- Neutrophils — one of the three types of granulocytes.
- Eosinophils — one of the types of the granulocytic lineage.
- Basophils — a type of granulocytes.
Class and exam questions
How does an HSC differ from a progenitor cell?
The HSC is pluripotent (can give rise to all blood cells) and indefinitely maintains its population. The progenitor cell is partially determined (oligopotent) and has a limited capacity for self-maintenance.
Starting from which class can blood cells be recognized under a microscope?
Morphological differences appear starting from Class IV (blasts). Cells of Classes I–III are externally identical and resemble small lymphocytes.
What is a CFU?
Colony-forming unit. This is an early hemopoietic cell (classes I–III) capable of proliferation and forming a clone (colony) consisting of numerous progeny.
What else to study on this topic
- Detailed analysis of myeloid lineage differentiation (CFU-GEMM and its derivatives)
- Two stages of unipotent cells of the erythroid lineage (BFU-E and CFU-E)
- Morphological features of blasts (Class IV)
- Features of asymmetric division of stem cells
- Humoral regulation of hemopoiesis by interleukins and poietins
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