What Are Myeloid Stem Cells? Including Definition, Derivation, And Differentiation

Also known as myeloid progenitor cells, these myeloid stem cells are a derivation of hematopoietic stem cells, and undergo differentiation to help produce the precursors of platelets, dendritic cells, erythrocytes, mast cells, granulocytes, and monocytes.

In comparison to their precursor, these stem cells have more restricted development potential and are thus capable of potentially giving rise to only seven different cell types.

As a result of this, they are classified as oligopotent progenitors. The key molecules that are involved in the process of differentiation of myeloid stem cells are:

• Interleukin 3
• Interleukin 5
• Granulocyte colony-stimulating factor (abbreviated to G-CSF)
• Agranulocytic-colon stimulating factors (abbreviated to AG-CSF)

Myeloid stem cells can also be referred to as Colony-forming unit granulocyte, erythroid, macrophage, megakaryocyte, or CFU-GEMM, and are often characterized by CD34, CD-64, and HLA-DR Markers. 

For the most part, stem cells that are a part of the myeloid stem cells lineage tend to be produced through the bone marrow intermediaries, but some studies have actually shown that some of these cells can directly develop from progenitors of the yolk sac. 

Monocytes And Macrophages

Monocytes are just some of the cells produced through the myeloid stem cell lineage.

Studies have shown that the cytokine – or the macrophage colony-stimulating factor (M-CSF) actually influences the proliferation of myeloid stem cells upon their differentiation, which helps to produce monoblasts that then differentiate further to help to produce function monocytes.

Cytokine is under the regulation of the transcription factors like ETS and AP-1. And cytokines such as M-CSF are typically released as a response to given stressors or infections.

The other signalling molecules that are often associated with this process are shown to include both interleukin 3 and interleukin 5.

In the case of an infection, or under stress conditions, monocytes and macrophages (which are monocytes that bring blood to reside in tissue across the body) help by producing M-CSF which in turn activates the differentiation process. Thus, more monocytes are produced from the myeloid stem cells. 

Studies have shown that these cells that produce M-CSF (The macrophages and monocytes) are influenced by various factors, which include GM-CSF, interleukin 3, as well as TNF-Alpha amongst other factors. 

Granulocytes

Included in Granulocytes are the white blood cells that are often characterized by small granules (proteins) that reside in their cytoplasm, which include neutrophils, basophils, and eosinophils.

All of which originate from the derivatives of the myoblast, which originated from the myeloid stem cells.

There are several factors that can contribute to the differentiation of the myeloid stem cells that produce myoblast, including:

• G-CSF (Granulocyte colony-stimulating factor)
• Interleukin 3
• Interleukin 5

Within healthy individuals, the serum is found to contain low levels of G-CSF. The expression of this factor in the serum is then increased however in the case of an infection, which in turn will increase the number of granulocytes.

Similar to mature neutrophils, the myeloid stem cells have receptors for G-CSF. As the increase of this factor occurs, myeloid stem cells have displayed signs of undergoing proliferation before then differentiating to produce myeloblasts.

This process is then repeated further in the new progenitors which will ultimately result in the product of mature granulocytes. 

The increased expression of G-CSF is also influenced by numerous factors, some of which are interleukin 1β, the tumor necrosis factor-alpha, and lipopolysaccharide.

For instance, in the presence of LPS, macrophages have been seen to release G-CSF, which therefore increases the level of this factor within the serum.

This increase is then detected by the myeloid stem cells, increasing proliferation and differentiation which ultimately results in the increased production of neutrophils as well as other granulocytes. 

Megakaryoblast

The megakaryoblast is a particularly large progenitor cell that undergoes differentiation and then gives rise to thrombocytes (platelets).

This is similar to the case with monoblast, which gives rise to monocytes as well as myeloblast, which then gives rise to granulocytes, megakaryoblasts are also a descendant of the myeloid stem cell lineage. 

The differentiation of the megakaryoblast is influenced by the cytokine thrombopoietin, with the production occurring in both the liver and the kidneys.

The process known as megakaryopoiesis is where the progenitors within the bone marrow give rise to the mature megakaryoblast, with thrombopoietin (TPO) being one of the more important cytokines that are involved in this process.

Once the cytokines have bonded to their receptors (MpI) that reside in the hematopoietic precursors, research has shown that they have a part to play in influencing differentiation throughout the megakaryocytic lineage.

The receptor has also been shown to exist in the megakaryocyte-erythroid progenitor (MEP), but not in the myeloid progenitors. 

As mentioned previously, this cytokine thrombopoietin is produced in both the liver and the kidneys, and is then released into the plasma.

This increased level of cytokine in the circulation can influence the actions of cells that have MpI receptors present, including hematopoietic stem cells, megakaryocyte-erythroid progenitors, and myeloid stem cells.  

How Do Myeloid Stem Cells Develop?

The development of myeloid stem cells originates from hematopoietic stem cells (These are just multipotent stem cells) in the red bone marrow, and are known for their responsibility of replenishing all of the blood cell types in the human body.

It was initially theorized that these hematopoietic stem cells could renew themselves through both symmetrical and asymmetrical cell division, which has been shown to be true after various amounts of research over the past few years.

The two forms of division have differing results. Symmetrical cell division results in two identical stem cells, whereas asymmetrical division produces a single stem cell – which is the same as the parent cell – as well as a differentiated cell. This differentiated cell is usually either a myeloid stem cell or a lymphoid stem cell. 

The process of development of a myeloid stem cell from a hematopoietic stem cell is named myelopoiesis. There are a number of important steps involved in this process, all of which are regulated by transcription factors such as PU.1.

The transcription factors involved in this process help influence the expression of the myeloid-specific genes and therefore the commitment of the cells to the myeloid lineage (Which is known as lineage bias).

Furthermore, they help regulate the differentiation of the myeloid stem cells to the progenitors that give rise to more specialized cells eventually. 

PU.1, is one of the transcription factors involved in the development of myeloid stem cells and is also known as Spi-1.

It belongs to the Erythroblast Transformation Specific (ETS) family and helps to target numerous genes, including the GM-CSF receptor alpha, the G-CSF receptor, and the integrin CD11B, as well as other genes too. 

Research using mice has shown that without this transcription factor, there is actually an absence of granulocytes and monocytes, which is evidence that this transcription factor plays a large role in the differentiation of the hematopoietic stem cells across the myeloid stem cell lineage.

This isn’t the only factor involved in the development of myeloid stem cells however, a few of the other factors that are important are:

• The core-binding factor family
• The EBD family
• The retinoic acid

Differentiation

Differentiation is essentially the process in which a cell (whether unspecialized or partially specialized) matures into a more specialized cell.

The best example of this is mentioned above, which is the development/maturation of the hematopoietic cells into myeloid stem cells. 

It has been theorized that some animals are capable of self-renewal of the progenitor cells, however, studies have shown that this tends to be rather limited, and can only occur seven days after they are initially produced.

Despite this, they can rapidly proliferate and differentiate, which gives rise to the progenitors that then go on to give rise to the specialized blood cells. 

It’s important to note however that the balance that is between proliferation and differentiation of the hematopoietic stem cells into progenitor lineages is actually governed by various transcription factors. 

Erythropoiesis And Differentiation Of Myeloid Stem Cells

Erythropoiesis is the process by which red blood cells are produced, this is a natural process that is done to replace the damaged or dead cells (Which can happen naturally or through infections such as malaria), it is also sometimes influenced by other conditions, such as anaemia or hypoxia for example. 

If these conditions occur, a cytokine which is known as erythropoietin is produced in the kidney, which then helps the production of red blood cells in the bone marrow. 

There are several incredibly important steps within this process, some of which include:

• The activation of the hematopoietic stem cells: Similarly to other cells, the production of red blood cells begins with the activation of the hematopoietic stem cells which are located inside of the bone marrow and are shown to activate as a result of cell-to-cell interaction as well as soluble macromolecules too.

Once the initial activation has occurred, the cells then differentiate to produce the myeloid stem cells.

• The differentiation of the myeloid stem cells: This second step in the process is where the myeloid stem cells differentiate which in turn produce more differentiated progenitors.

The key role is played by the cytokine erythropoietin, which differentiates the myeloid stem cells to produce megakaryocytic or erythroid progenitors as well as granulocyte-myeloid progenitors on certain occasions.

• Differentiation of the megakaryocytic or erythroid progenitors: this step in the production of the red blood cells involves the proliferation as well as the differentiation of the megakaryocytic erythroid progenitors which then help to produce colony-forming units, which in turn are also capable of responding to the cytokine erythropoietin that is present.

Further differentiation is then undergone in order to produce progenitors which are known as erythroblasts, otherwise known as normoblasts, inside the bone marrow.

Normoblasts will lose a number of organelles as well as their nucleus as they begin to mature and transform into reticulocytes, which also lose more organelles as they finally mature into red blood cells.

What Is The Difference Between Lymphoid Stem Cells And Myeloid Stem Cells?

Both myeloid stem cells and lymphoid stem cells originate from the hematopoietic stem cell, and there a number of certain similarities as well as differences between the two cells, which are explained below:

Similarities

• Origins: As previously mentioned, both of these stem cells originate from the hematopoietic stem cell (which are the multipotent stem cells that are located within the red bone marrow).

This where the differentiation ultimately leads to two lineages, the lymphoid and the myeloid. Both of which then go on to further produce different types of cells.

• They are both oligopotent progenitors: Stem cells is the term predominantly used for these two cells, but they are actually also both progenitors.

So whilst they are still capable of differentiating to produce various different types of cells, both the cells are actually incapable of self-renewal (or are otherwise characterized by the limited self-renewal ability) and as such do not actually qualify as stem cells.

Therefore, as oligopotent cells, they can only help to give rise to several different types of cells in comparison to their precursors but do have a higher potency as a result.

• They are located in the bone marrow: Both myeloid stem cells and lymphoid stem cells can be located in the bone marrow in adults.

As well as other cells and progenitors, these two types of cells differentiate inside the bone marrow and help to produce low potency progenitors that can give rise to more mature functional cells.

These functional cells can then enter blood circulation to migrate to other tissues around the body, unlike stem cells and progenitors.

Differences

• Interleukin 7 Receptors: Perhaps the most notable difference between myeloid stem cells and lymphoid stem cells is the lack of the IL-7 receptor in myeloid stem cells. This receptor is expressed on lymphoid stem cells and plays a large role in the differentiation of the B and T cells lineage.

This receptor is completely absent in the myeloid stem cell, and as a result, is incredibly useful for scientists to differentiate between the two cells inside an organism.

• Lineage: Both lymphoid stem cells and myeloid stem cells originate from the same hematopoietic stem cells, however the cells’ lineage changes upon differentiation, proceeding upon separate lines and therefore resulting in the production of different types of cell to one another.

The presence of signalling molecules means that myeloid stem cells differentiate and produce progenitors that then go on to give rise to platelets, granulocytes, monocytes, and dendritic cells too.

In comparison, lymphoid stem cells differentiate to produce progenitors that produce lymphocytes, dendritic cells, and natural killer cells. Studies show that lymphoid lineage cells actually make up nearly 15% of the cells found in the bone marrow.

• Colony-Stimulating Factors: Within both the myeloid and lymphoid lineages, blood growth factors, otherwise known as colony-stimulating factors, are involved in the differentiation of progenitors, which in turn result in the production of functioning white blood cells.

The granulocyte colony-stimulating factor influences the differentiation of the myeloid stem cells, which then produce granulocytes, particularly neutrophils.

Whereas the agranulocytic colony-stimulating factor is involved in the lymphoid stem cell lineage, activating the production of the lymphocytes (B and T cells).

Frequently Asked Questions

There often some questions raised regarding myeloid stem cells, and the nature of stem cells in general, thankfully, this section will help aim to resolve some of these common queries surrounding the subject:

What Does Potency Mean In Stem Cells?

Cell potency is simply a measure of the ability that some stem cells have to differentiate themselves into various different specialized cell types. Cells that have a greater potency can generate more specialized cells than those that have a lower level of potency.

What Is Symmetric Division?

Symmetrical division in regards to stem cells simply means that the initial stem cell produces either differentiated stem cells or two stem cells that are exactly the same as the original stem cell, which is known as a cell with an equal fate.

During this process, the cell-fate determining factors are shared evenly across the two “daughter” cells, which are what produce equivalent cell fates.

What Is Asymmetric Division?

The asymmetrical division is a common characteristic of stem cells. Throughout the development of an organism, it is often asymmetrical division that dominates.

When a cell divides asymmetrically, it produces two “daughter” cells that have different cell fates, one is usually a stem cell, whilst the other is typically a differentiated cell.

The differentiated cell is the one in which carries on the lineage, whilst the other stem cell will continue to divide asymmetrically further. 

Why Are Myeloid Cells Important?

Ultimately, myeloid cells are incredibly important in the overall protection of the body. Their role is to help mount the immune system’s defences against any form of viruses.

They are also responsible for the detection of pathogen-associated molecular patterns, which helps the body to prepare itself for attack from the virus and to help mitigate the effects it has on a person. 

Why Study Stem Cells?

Studying stem cells helps scientists to understand the role that stem cells have to play in the development of some serious illnesses and conditions, such as birth defects and cancer.

Therefore, an expansive understanding of how these cells develop normally should help to indicate how these conditions develop and perhaps how they can be reversed and cured.

There is also the potential for cell therapy, which has the possibility to be used to treat a number of diseases and conditions or disabilities, such as burns, strokes, spinal cord injuries, and Parkinson’s disease.

Conclusion

In conclusion, myeloid stem cells are extremely important for the human body, and the processes that are involved in their development, their derivation, as well as their differentiation are all extremely complicated.

Hopefully, with the aid of this guide, you have been able to further understand myeloid stem cells, their positioning in comparison to lymphoid stem cells, as well as the similarities and differences between them both.

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