ERYTHROBLASTS: WHAT ARE THEY, ERYTHROPOIESIS, ASSOCIATED PATHOLOGIES - BIOLOGY - 2024

The erythroblasts are precursor cells of erythrocytes vertebrate. The decrease in oxygen concentration in the tissues will promote cellular differentiation events in these cells that will give rise to mature erythrocytes. The set of all these events is known as erythropoiesis.

During erythropoiesis, hemoglobin synthesis increases. An abundant protein in erythrocytes that mediates the delivery of oxygen to the tissues and the detoxification of carbon dioxide from them, a waste product of cellular respiration that is toxic to cells.

Stained smear of erythroblasts, precursor cells of mature erythrocytes. By The Armed Forces Institute of Pathology (AFIP), from Wikimedia Commons The total loss of the nucleus, as well as the cellular organelles, marks the culmination of the erythropoiesis process in mammalian vertebrate cells. In the rest of vertebrates such as reptiles, the nucleus persists once the differentiation process has finished.

Errors in the differentiation process of the erythroblasts give rise to a set of blood pathologies that together are called megaloblastic anemias.

What are erythrocytes?

Image of Erythrocytes obtained by holographic microscopy. By Egelberg, from Wikimedia Commons Red blood cells, commonly known as red blood cells, are the most abundant cells in vertebrate blood.

They have a characteristic morphology similar to biconcave discs and their main function is to carry out the transport of oxygen (O2) to the different tissues of the body, at the same time that it detoxifies them from the carbon dioxide (CO2) produced during cellular respiration..

This exchange of CO2 for O2 is possible because these cells harbor large amounts of a characteristic red protein called hemoglobin, capable of interacting with both chemical species through a heme group present in their structure.

A particularity of these cells in mammals with respect to the rest of vertebrates is the lack of nucleus and cytoplasmic organelles. However, during the initial phases of production in the early stages of embryonic development, it has been observed that the cellular precursors from which they originate present a transitory nucleus.

The latter is not surprising given that the early stages of embryo development are usually similar in all vertebrates, diverging only those stages that lead to greater differentiation.

What are erythroblasts?

Erythroblasts are cells that will give rise to mature erythrocytes after undergoing consecutive events of cell differentiation.

These precursor cells originate from a common myeloid progenitor in vertebrate bone marrow as nucleated cells, provided with nuclei and cellular organelles.

Changes in the content of its cytoplasm and in the rearrangement of the cytoskeleton will culminate in the generation of erythrocytes ready to enter circulation. These changes respond to environmental stimuli indicative of the decrease of oxygen in the tissues and therefore a demand in the production of erythrocytes.

What is erythropoiesis?

Erythropoiesis is the term used to define the process by which the production and development of red blood cells, necessary to maintain the oxygen supply to the different organs and tissues, takes place.

This process is finely regulated by the action of erythropoietin (EPO), a renal synthesis hormone that in turn is modulated by the oxygen concentrations available in the tissues.

Low concentrations of tissue oxygen induce the synthesis of EPO by the hypoxia-inducible transcription factor (HIF-1), which stimulates the proliferation of erythrocytes by binding to EpoR receptors, present in erythrocyte precursor cells.

In mammals, erythropoiesis is carried out in two stages that are called primitive erythropoiesis and definitive erythropoiesis.

The former occurs in the yolk sac during embryonic development giving rise to large nucleated erythroblasts, while the latter occurs in the fetal liver and continues in the bone marrow after the second month of gestation, generating smaller enucleated erythrocytes.

Other proteins such as the antipoptotic cytokine Bcl-X, whose transcription is regulated by the transcription factor GATA-1, also positively influence the erythropoiesis process. In addition, the supply of iron, vitamin B12 and folic acid are also necessary.

Differentiation of erythroblasts into erythrocytes

In the process of definitive erythropoiesis, erythrocytes are formed in the bone marrow from an undifferentiated progenitor cell or common myeloid progenitor capable of giving rise to other cells such as granulocytes, monocytes and platelets.

This cell must receive the appropriate extracellular signals to compromise its differentiation into the erythroid lineage.

Once this commitment is acquired, a sequence of differentiation events begins that begins with the formation of the pronormoblast, also known as the proerythroblast. A large erythroblast precursor cell with a nucleus.

Subsequently, the proerythroblast will experience a progressive decrease in nuclear cell volume accompanied by an increase in hemoglobin synthesis. All these changes occur slowly as this cell passes through different cell stages: the basophilic erythroblast or normoblast, polychromatic erythroblast, and orthochromatic erythroblast.

The process concludes with the total loss of the nucleus, as well as of the organelles present in the orthochromatic erythroblast, causing a mature erythrocyte.

To finally reach this, the latter must pass through the reticulocyte stage, an enucleated cell that still contains organelles and ribosomes in its cytoplasm. The complete elimination of the nucleus and organelles is carried out by exocytosis.

Mature erythrocytes exit the bone marrow into the bloodstream where they remain circulating for approximately 120 days, before being swallowed by macrophages. Therefore, erythropoiesis is a process that occurs continuously throughout the life of an organism.

Cell differentiation

As erythoblasts progress toward complete differentiation into a mature erythrocyte, they undergo multiple changes in their cytoskeleton, as well as in the expression of cell adhesion proteins.

Actin microfilaments depolymerize and a new spectrin-based cytoskeleton is assembled. Spectrin is a peripheral membrane protein located on the cytoplasmic face that interacts with ankyrin, a protein that mediates the binding of the cytoskeleton with the Band 3 transmembrane protein.

These changes in the cytoskeleton and in the expression of Epo receptors, as well as the mechanisms that modulate them, are critical for erythroid maturation.

This is due to the fact that they mediate the establishment of interactions between erythroblasts and cells present in the bone marrow microenvironment, facilitating the transmission of the necessary signals to begin and end differentiation.

Once the differentiation is finished, new changes occur that favor the loss of adhesion of the cells to the marrow and their release into the bloodstream where they will fulfill their function.

Pathologies associated with errors in erythroblast differentiation

Errors during the differentiation of erythroblasts in the bone marrow give rise to the appearance of blood diseases, such as megaloblastic anemias. These originate from deficiencies in the supply of vitamin B12 and folates necessary to promote erythroblast differentiation.

The term megaloblastic refers to the large size that erythroblasts and even erythrocytes reach as a product of ineffective erythropoiesis characterized by defective DNA synthesis.

References

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