It was during my studies in Medical School. We were covering Histology and Cell Biology. Many terms were flying around making it difficult to get an adequate grasp of the various cell lines that originate from the Pluripotent Stem cell. It was amazing to concept to consider. One cell, the all-in-one component, that had no clear identity, yet possessed everything it needed to become ANY cell type the body required. I sat at a restaurant reviewing my notes when a model came to my head. I began drawing on napkins when this model emerged. It has proven useful for many years and helps me understand this subject better as topics about stem cells, leukemia and anemia are discussed.
Allow me to share a short overview through a series of images I reproduced from those sketches. Later I will share some defining aspects of this model and how this model proves useful in grasping all Leukemia, stem cell studies, and blood disorders clearly,and easily.
The Top of the Pyramid is the Stem Cell. It is also called Pluripotent, because it has the potential to become ANY cell that the body requires. Now every cell in the body has your genetic code, in other words every cell reads the same blue prints. However, these blue prints have many pages, so that each cell at the time of their defining moment will be told what page they should read. This is made possible by the messages conveyed to each cell. After receiving their primary instruction, they begin to produce small translating proteins governed by a factory inside the nucleus. These small proteins will help unfold a specific condensed coil of DNA (blueprints) and twist it out in the open sea of transcribing proteins. These proteins will then start the initial modifications which gives the cell an identity and function. So every cell reads the same DNA, but their identity is determined by what part of the code it reads. Beautiful, isn’t it?
Anyway, back to the model. You will see three main path directions the stem cell can roll down the pyramid. It can roll to the right towards the Red Blood cell pathway, to the left towards the Lymphocyte pathway or toward the front which is the Granulocytic pathway.
Now, here allow me to pause and mention that all cells carry their DNA through their lifetime, EXCEPT for Red Blood Cells (RBC). The reason is because their role is so clearly defined at maturation that they no longer require the blueprints. Furthermore they do not have the room to carry the unnecessary machinery if they are to use as much space as they can for Hemoglobin, to carry needed oxygen to your tissues and organs. Their role on life’s stage is about 3 months anyway, so they need to be optimal for a short time before they are recycled.
You may be wondering how the pluripotent stem cell knows which side to roll down? Well, as the cell begins the early stage of development, signals are provided from the instructions of your body needs. This tells the DNA to unfold just in certain areas which instruct the proteins inside the cell to form small “foot” receptors for cell mobility. These foot receptors stick outside the cell wall and snap into certain floor stepping stones which tilt the balance toward that edge. Then as the cell begins it’s roll down the descending wall, it makes contact on the specified textured side stones, which provides further signaling to the cell machinery. This helps to explain how the developing “foot”processes form, directing the undefined character of the cell toward further differentiation and identity.
Lets look at the next slide.
In this slide, you are standing above the model. I provided a map to summarize what I have already discussed.
This slide shows the lymphocytic side of the model. Notice, that I have labeled a textured stone as CD19. This is a cytologic marker which is on every lymphocyte. This is an example of the type of stepping stone that helps ambulate the unique foot process of a defining lymphocyte. As I continue to gather more data, I plan to further develop the stepping stones or cell markers that characterizes each cell type.
Now as the lymphocyte rolls further down it will differentiate further. Let us move to that slide.
Here we have the next branch of maturation for lymphocytes. They will become either T-cell or B-cells. Their role is to police infection , but their tasks are different. They may become presenter cells (to show foreign material to infection station, or some even become Killer cells. These cells are like a Highway Patrol, which frisks passing cells during their travels and pulling random cells over that look suspicious. If there is a cause of concern, the Killer cells have authority to activate a self destruct button on that cell. This is important as such cells may be harboring a virus hidden away inside it’s machinery.
Under the right signal conditions, the B-cell proliferates and becomes a Plasma cell. These plasma cells become powerful micro-factories and takes on the task of generating “target-specific rockets”, designed to eliminate foreign saboteurs. Tons of these special rockets are sent out to move along with the traffic increasing the likelihood of bumping into it’s target, if it exists.
There are a wide range of important functions here. I can discuss this in a future blog.
However, I do wish to point out that I made the developmental parts of each lymphocyte branch as stairs for a reason. Sometimes there are stages in cell development where it is more sensitive to specific infections.Such is the case for Burkitt’s Lymphoma, It seems to attack B-cells during the intermediate stage of development. Therefore in including this added feature to my model, it helps me to remember that this set of stairs are clinically significant.
The front platform is the granulocytic side of the pyramid. The stem cell rolls toward this path because of a signaling messenger call Granulocyte Stimulating Factor (GSF). As it rolls toward the front it becomes further differentiated into various white cells. To clarify an earlier point, if GSF is present and the cell rolls this direction, it may receive a signal from Interleukin-5. If it has the correct receptors, these cells will tilt and drop off as Eosinophils. I must go but I hope to share more later. I hope my model proves useful to you the reader..
Thanks for reading.
Greg E. Williams, MD
See Animated Video of this model: