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Totipotent, Pluripotent and Multipotent Stem Cells – What is the Difference?

Totipotent, Pluripotent and Multipotent Stem Cells – What is the Difference?

In this post let us talk about few terms that we frequently use when we talk about stem cells and they can be really confusing sometimes. I am talking about totipotent, pluripotent and multipotent. Like always first thing first. What are stem cells? Stem cells are undifferentiated, unspecialized cells which mean stem cells can differentiate into any type of cell present in our body and we have around 200+ cell types in our body and stem cell can give rise to any of them.

To understand these three terms we should know the categories of stem cells. Stem cells are classified under two categories, embryonic stem cells – found in embryo and adult stem cells – found in many organs. Embryonic stem cells can be either totipotent or pluripotent and adult stem cells are multipotent.

Now once let us try and understand each of the term.

  1. Totipotent – “totus” means “whole”. So the term is about whole of something. To understand totipotency let us go to fertilization process. When sperm cell fertilizes an egg it results in the zygote formation, we all know that. This zygote will then start dividing and differentiating, giving rise to whole organism. So this ability of zygote that it can differentiate into any type of cell (making a complete organism) is called totipotency. That means a zygote is a cell which is totipotent.
  2.  Pluripotent – “pluri” means “several”. Now once the zygote is formed, it will start dividing and after few divisions it will reach the blastocyst stage. At this stage it is a hollow ball which has a cluster of cells called inner cell mass and a single cell line at the periphery called trophoblast. The inner cell mass of the blastocyst has the ability to produce all the cell types of our body except for what trophoblast can form e.g., placenta, amniotic sac etc. So this means we have around 200+ cell types in our body and inner cell mass can differentiated into any of them, e.g., it can give rise to all the blood cells, cardiac muscles, neural cells. This ability of inner cell mass is called pluripotency. So inner cell mass cells are pluripotent and we wouldn’t call it totipotent because it cannot give rise to what trophoblast cells can.
  3. Multipotent – “multi” in this case means “few”. As in the classification we saw that multipotent is term related to adult stem cells. Adult stem cells are found in many organs which means they are already specified to differentiate in particular cell line, depending on which organ they are present in. To make it easier to understand let us compare it with pluripotent stem cells. Pluripotent cells, as we already establish can differentiate in any of the cell type but multipotent cell would be more specified for one or more cell lines e.g., mesenchymal stem cell differentiates to form bone, cartilage, connective tissue, adipose tissue etc. So mesenchymal stem cell is multipotent.

Hope I am able to make it clear to you guys:)

Watch a video on this topic here.

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Hematopoiesis – Overview [Blood Cell Formation]

Hematopoiesis

Hematopoiesis, also known as Hemopoiesis is formation and development of blood cells. Meaning of the term hematopoiesis is “Hemo = blood” and “poiesis = to form”. Hematopoiesis occurs in bone marrow and where is this bone marrow located?? To understand this, let us take a cross section of a bone (figure a).

Figure a. Bone Marrow

In figure a we can see the center cavity of bone has the red spongy tissue. This red spongy tissue in the center of the bone is called bone marrow. OK so we are clear with some terminology and we will see few more as we go on J

The starting point of Hematopoiesis is Hematopoietic Stem Cell (HSC) which is a multipotent stem cell. What is multipotent now?? The meaning of multipotent is “multi = many” and “potent = being able” which means the cell has ability to differentiate or give rise to several different types of cells. We will see how HSC which is a pluripotent stem cell gives rise to all different types of blood cells (figure b).

Figure b. Hematopoiesis

The first differentiation of HSC results in two lineages – Myeloid stem cell and Lymphoid stem cell. Now let me tell you couple of points which would make this chart (figure b) very easy to understand and remember.

First, the lymphoid stem cell lineage gives rise to all the lymphocytes and the myeloid stem cell will differentiate in rest of the blood cells (other than lymphocytes). Lymphoid stem cell = all lymphocytes, easy to understand and remember J Second, once the main two lineages are differentiated (myeloid and lymphoid), it will now differentiate into progenitor cells (green in color in fig b), followed by differentiation in precursor cells (blue in color in fig b) which are named by writing suffix “blast”, i.e. proerythroblast, megakaryoblast, monoblast etc. Now this precursor cells will undergo further development and becomes formed element (red in color in fig b).

So briefly it is,

 HSC – myeloid and lymphoid lineages – progenitor cells – precursor cells – formed elements  

Now that we are clear with these points, keeping them in mind let us see the differentiation process.

So first we will see what happens to myeloid stem cell. It will differentiate into Colony Forming Unit – Erythrocyte (CFU-E), Colony Forming Unit – Megakaryocyte (CFU-Meg) and Colony Forming Unit – Granulocyte and Macrophage (CFU-GM). If you look at these progenitor cell, you can understand what it is going get developed in. There are two more cell developing from myeloid cell but they don’t have progenitor cell phase, it will have direct precursor cell stage.

Alright so now once the progenitor cells are formed, the next stage is the formation of precursor cells. As I mentioned before they will have suffix “blast”. So from CFU-E, proerythroblast will form. From CFU-Meg, megakaryoblast will form. From CFU-GM two precursor cell will form as the term suggest, monoblast and myeloblast. And as I said there will be two more precursor cells directly differentiating from myeloid stem cell and they are eosionophilic myelolast and basophilic myeloblast.

Now proerythroblst is going to get developed in reticulocyte, at this point the nucleus of RBC will be ejected and eventually it will developed in erythrocyte (RBC). Megakaryoblast will differentiate in a huge megakaryocyte cell which gets splinter into thousands of small fragments and that is what we call thrombocyte (platelets). Monoblast differentiates into monocyte and circulating monocytes are called macrophages. The remaining three precursor cells are going to give rise to all granulocytes and if you notice that all the precursor cells of granulocyte are named myeloblast, i.e. myeloblast will developed into neutrophil, eosionophilic myeloblast will developed into eosinophil and basophilic myeloblast will developed into basophil.

Now let us see what happens to lymphoid stem cell. It will differentiate into two progenitor cells, i.e. prothymocyte and pre B-cell and they will develop into precursor cells T lymphoblast and B lymphoblast respectively. Here also there is one direct precursor cell formation without the progenitor cell stage and that is NK lymphoblast (again see suffix “blast” in all precursor cells). T lymphoblast will develop into T lymphocyte (T cell), B lymphoblast will develop into B lymphoblast (B cell) and NK lymphoblast will give rise to Natural killer cell (NK cell).

So that is it!! It is very easy to understand once we know all different stages and how they are named. Last but not least this is how you can remember it 🙂

First, you start with HSC which give rise to two lineages myeloid and lymphoid and here the term itself has the answer that lymphoid stem cell give rise to all lymphoid cells which include T cells, B cells and NK cells. All other remaining blood cells are derived from myeloid stem cell.

Second, progenitor cells are formed and in case of eosinophil, basophil and NK cell there is no progenitor cell.

Third, the progenitor cells differentiates into precursor cells (suffix “blast”) which then differentiates in to formed elements and they are nothing but our blood cells.

For better understanding watch this video on Hematopoiesis.