Progenitor Cells

Definition, Types, Vs Stem Cells and Function


Definition



Essentially, progenitor cells have been described as stem cell descendants with the limited ability to self-renew, proliferate, and give rise to more specialized cells. In the human body, the number of progenitors only makes up a minor proportion of the total population of cells.

They have been shown to reside in various tissues in the body where are capable of differentiating into one or more lineages. Because of their capacity for self-renewal, proliferation, and differentiation, progenitor cells also play an important role in repair and regenerative processes.

 

* While progenitor cells are descendants of stem cells, they are not sufficiently differentiated to perform specific functions. For this reason, they are described as intermediates between stem cells and the more specialized and functional cells of the body. 


* Most progenitor cells are characterized by a large nucleus to cytoplasm ratio. Moreover, they contain a limited number of organelles involved in such functions as cell development and division.




Types of Progenitor Cells




As mentioned, progenitor cells can be found in different body tissues. In different types of animals/organisms as well as human beings, these cells can give rise to different types of specialized cells, capable of performing specific functions.

Generally, progenitor cells found in different parts (tissues) of the body can be classified into several categories based on cell potency. 


These include:



Multipotent Progenitor Cells



Of all the different types of progenitor cells, multipotent progenitors are closest to stem cells. This is because compared to the other progenitors, they have a relatively higher capacity for self-renewal as well as the ability to give rise to more different types of specialized cells (several lineages). 

While there are a number of multipotent progenitor cells, this section will focus on two main types. 



These include:

 

Multipotent hematopoietic progenitor cells

 

Referred to as hematopoietic stem cells in some books, multipotent hematopoietic progenitors are commonly found in the bone marrow. However, they have also been detected in the liver, spleen, and peripheral blood. 

Like other progenitor cells, these cells originate from stem cells that are capable of self-renewal and differentiation. In mice, studies have shown hematopoietic stem cells to give rise to multipotent progenitors that are only capable of self-renewal for no more than 2 weeks. 

Here, it's also worth noting that the stem cells (short term hematopoietic stem cells) that give rise to the multipotent progenitors originate from another group of stem cells known as long term hematopoietic stem cells.

In addition to the reduced capacity for self-renewal, multipotent hematopoietic progenitor cells, as well as short term stem cells, are also incapable of differentiating to produce long term stem cells. 

Once they are activated, multipotent hematopoietic progenitors differentiate to produce common myeloid progenitors or common lymphoid progenitors. Here, the lineage to which these cells (multipotent progenitors) commit is dependent on the type of signaling molecules. 

 


Liver progenitor cells 

 

Liver progenitor cells found in the bone marrow are also multipotent progenitors. They are oval-like cells that were first identified in the 1930s. Characterized by markers like CD34, these cells have been shown to give rise to various hepatocytes and hepatocyte-like cells.

For this reason, they have been transplanted to help repopulate liver cells in patients especially in cases of liver damage. 

 


Oligopotent progenitors 

 

The second group of progenitor cells is known as oligopotent progenitors. Given that they originate from multipotent progenitors, these progenitor cells are more differentiated and thus more specialized compared to multipotent progenitors.

For this reason, their self-renewal capacity is significantly reduced compared to stem cells and multipotent progenitors. However, they can proliferate and differentiate to give rise to a few cell types.


Some of the most common oligopotent progenitor cells include:

 


Corneal epithelial progenitor cells

 

Found within the peripheral/limbal zone of the cornea, corneal epithelial progenitors have been shown to be oligopotent cells involved in the renewal of the corneal epithelium. The loss of these cells has been associated with gradual blinding - a condition that is known as limbal stem cell deficiency.

 


Myeloid progenitor cells and lymphoid progenitor cells

 

Common myeloid and lymphoid progenitor cells are the products of multipotent hematopoietic progenitor cells. As such, they are some of the most common and well-studied oligopotent progenitor cells. When they are stimulated, these progenitors rapidly proliferate and differentiate to produce a number of cells.

For instance, whereas the lymphoid progenitor lineage gives rise to the lymphoblast, the precursor to T lymphocytes, the myeloid progenitor gives rise to cells like the myeloblast (the precursor to granulocytes, etc.). 

 

* The potency of oligopotent cells is limited when compared to multipotent cells and stem cells. Here, then, stem cells are involved in the production of progenitors that ultimately give rise to differentiated and functional cells.

 

* Like their precursors, myeloid and lymphoid progenitors (oligopotent progenitors) are also located in the bone marrow. Cells produced through these lineages ultimately migrate and enter circulation from where they can perform specific functions.

 


Bipotent Progenitor Cells


Bipotent progenitor cells are progenitors that can differentiate to produce two types of cells following activation. 


Some examples of bipotent progenitors include:

 

Hepatic progenitor cells - Hepatic progenitor cells located in the liver have been shown to be bipotent. The proliferation of these cells has been shown to play an important role in the regeneration process as well as primary liver cancers. 

 

Bipotent progenitors of the mammary epithelium - Bipotent progenitors are some of the cells found in the human mammary gland. In vitro, these cells are characterized by their ability to produce type I and type III luminal and myoepithelial cells. 



Unipotent Progenitor Cells


 

Unipotent progenitor cells may be described as the type of progenitors that produce one type of cell (differentiated and specialized cell). Compared to their precursors, the potency of unipotent progenitors is further reduced which limits the type of functional cells they can produce.

In looking at the non-stem cells/non-progenitor cells they produce, they have been shown to have some capacity for self-renewal. 

 

Although there had been debates as to whether true unipotent progenitor cells exist, a number of cells in the body are classified as unipotent progenitors.


Some examples of cells considered to be unipotent progenitors include:

 

Muscle stem cells


As compared to embryonic stem cells, the muscle stem cells are adult stem cells found in the skeletal muscle tissue. Compared to cells of the skeletal muscle, these muscle stem cells are capable of self-renewal and differentiation.

Like many other progenitors, these cells are characterized by a large nucleus and little cytoplasm. However, they also contain several organelles involved in various cellular processes. 

 

Monoblast - Monoblasts are some of the largest cells involved in hematopoiesis. Located in the bone marrow, monoblasts are characterized by a spherical morphology, a large nucleus (centrally located) as well as a grainy cytoplasm.

Differentiation of the cell results in the production of monocytes

 

Myeloblast - Like the monoblast, the myeloblast is also a descendant of the myeloid progenitor cells. It's also located in the bone marrow and differentiates to produce granulocytes. 

 


Progenitor Cells Vs Stem Cells



Stem cells are a special type of undifferentiated (or partially differentiated) that can give rise to a variety of cells in the body.



In general, there are three characteristics associated with these cells which include:

 

Undifferentiated (or partially differentiated)

 

One of the main characteristics of stem cells is that they are undifferentiated and thus not fully committed to a given path/lineage of specialized cells. By observing pluripotent stem cells, for instance, researchers have reported that compared to other more specialized cells, these cells do not exhibit such tissue-specific characteristics like morphology and gene expression. 

For this reason, they cannot perform any specialized function compared to other specialized cells like epithelial cells, hepatocytes, and myocardiocytes, etc. 

 

* Some stem cells, especially most adult stem cells are partially differentiated.



Capable of self-renewal (proliferation)

 

The other primary characteristic of stem cells is their ability to proliferate (self-renewal). This refers to the ability of stem cells to make more stem cells which allows for a given number of stem cells to be maintained.

Here, this may be achieved through symmetrical or asymmetrical division. While symmetrical division results in the formation/production of two identical stem cells, asymmetrical division produces one stem cell and a differentiated cell. This, however, is largely dependent on the presence or absence of signaling molecules. 

 

Differentiation 

 

Cell differentiation may be described as the development of a cell to produce a more specialized cell. While stem cells are undifferentiated, they have the capacity to become any type of cell in the body.

Compared to partially differentiated stem cells, undifferentiated stem cells can give rise to a wide range of specialized cells. For this reason, they have generated significant interest from the scientific community. 

 


Types of Stem Cells



There are several types of stem cells which include:

 

Embryonic stem cells - As the name suggests, these are the types of stem cells obtained from the early stages of an embryo. They are pluripotent cells that develop to produce cells of the three primary germ layers. As such, they can differentiate to produce any cell type in the body. 

 

Adult stem cells - Compared to embryonic stem cells, adult stem cells are partially differentiated. They are classified as multipotent cells and therefore give rise to several types of cells in the body. These cells are particularly important given that they help replace damaged and dying cells.

Some examples of adult stem cells include hematopoietic stem cells and epithelial stem cells. 

 

Induced pluripotent stem cells - Compared to the other stem cells, induced stem cells are produced in the laboratory so that they can be used to produce any type of cell required. 

 

While the terms progenitor cells and stem cells are sometimes used interchangeably, the two types of cells are different with several differences and similarities. 

 




Similarities between Progenitor and Stem Cells



Differentiation - One of the main similarities between progenitor cells and stem cells is the fact that they are both capable of differentiating. Once they are activated by specific signaling molecules, both types of cells undergo differentiation and ultimately give rise to specialized cells that perform specific functions. 

 

Self-renewal - Some progenitor cells (like endothelial progenitor cells) have been shown to have some capacity for self-renewal. For most progenitor cells, however, this ability is significantly limited 

 


Differences between Progenitor Cells and Stem Cells



Longevity - One of the main differences between progenitor cells and stem cells is that stem cells have a longer lifespan compared to progenitor cells. Based on a number of studies, stem cells have been shown to have a life span ranging from several months (about 5 months) to over three years.

Progenitor cells, on the other hand, rapidly proliferate and differentiate to produce more specialized cells with very limited capacity for self-renewal. For this reason, they have a shorter life span. 

 

Self-renewal - While some of the progenitor cells have been shown to have the capacity for self-renewal, this is limited to a few days. Stem cells, on the other hand, have a higher capacity for self-renewal which not only allows for a given number of stem cells to be maintained, but also continue giving rise to various functional/specialized cells.

 

Differentiation - While both progenitor cells and stem cells are capable of differentiation, progenitor cells are partially differentiated while stem cells are undifferentiated. For this reason, stem cells can give rise to more cell types than progenitor cells. 

 

Origin – As mentioned, stem cells are pluripotent cells found in the blastocyst (embryo). Progenitor cells are descendants of the stem cells. As such, they are partially differentiated compared to their precursors which are not differentiated.

In adults, stem cells located in different regions of the body continue giving rise to various progenitors which in turn produce more specialized cells. 


Functions of Progenitor Cells



They replace dead or damaged cells

 

As intermediates between stem cells and specialized cells, one of the main functions of progenitor cells is to replace dead and damaged cells. In the small intestine, for instance, studies have shown epithelial cells to be replaced every six (6) days.

Here, the rapidly dividing progenitors give rise to new epithelial cells thus replacing the cells damaged from the constant wear and tear. In the case of anucleated cells like red blood cells, which cannot undergo mitosis (cell division), progenitor cells are especially important given that they continue to develop as new specialized cells. 

 

Immune responses

 

In the presence of given signaling molecules, progenitor cells (hematopoietic progenitor cells) increase the population of given immune cells in response to invading microorganisms or foreign substances.

In this case, the primary function of progenitor cells is to increase the population of immune cells so that they can effectively clear off the invading pathogens as well as damaged cells. 

 

Progenitor cell-based therapy 

 

With a better understanding of how stem cells and progenitor cells work, researchers have been working on how to use these cells for the purposes of treating various conditions and diseases (e.g. cardiovascular disease).

Recently, for instance, scientists were able to regenerate the damaged spinal cord nerve fibers of a paralyzed mouse allowing it to walk again. 

 

 


See also: Endothelial Progenitor Cells, Neural Progenitor Cells


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References



Jonathan Slack. (2012). Stem Cells: A Very Short Introduction. 

 

Judith A. Shizuru, Robert S. Negrin, and Irving L. Weissman. (2005). Hematopoietic Stem And Progenitor Cells:Clinical and Preclinical Regeneration of the Hematolymphoid System.

 

Peter Siig Vestentoft. (2014). Adult Hepatic Progenitor Cells. 

 

Verónica Martínez-Cerdeño and Stephen C. Noctor. (2018). Neural Progenitor Cell Terminology.

 

 

Links 

 

https://www.technologynetworks.com/cell-science/articles/what-are-progenitor-cells-exploring-neural-myeloid-and-hematopoietic-progenitor-cells-329519


https://stemcells.nih.gov/info/basics/II.htm


https://bigthink.com/surprising-science/spinal-cord-paralysis-breakthrough