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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.

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Agrobacterium – Nature’s own genetic engineer!!

Agrobacterium – Nature’s own genetic engineer!!

Agrobacterium is nature’s beautiful creation and it is nature’s own genetic engineer. This microscopic genius has the ability to transfer its gene to plant and this property has made Agrobacterium very popular in the field of genetic engineering. Because utilizing this property scientists are able to obtain improved quality plants.

Agrobacterium is Gram negative soil bacteria and when it infects plant i.e. when it transfers its gene to plant, the plant develops Crown Gall disease. So in this post we will see the important genes involved in the transfer and of course at the end I will share my trick to remember which gene does what function. So let’s get started 🙂

Agrobacterium’s gene transfer property is within its plasmid called Ti plasmid. Ti stands for Tumor Inducing.

Figure a shows the important segments of Ti plasmid which are as followed.

  1. Ti plasmid has T-DNA region which is transfer region and it is the only part which gets transfer from bacteria to plant. This T-region contains auxin production, cytokinin production and opine synthesis genes.
  2. Ti plasmid also has virulence region which is require to mediate the gene transfer. This region includes genes such as vir A, vir B, vir G, vir C, vir D and vir E.

Mechanism of Gene Transfer :

  •   When a plant gets injured (may be by insect bite), it causes secretion of phenolics such as acetosyringone from plant. This acetosyringone acts as attractant for Agrobacterium. As a result, lot of Agrobacterium would get attracted towards the wounded region of the plant.
  •   Acetosyringone activates the vir A which is a transmembrane protein by autophosphorylating it. Once vir A is activated it activates vir G by phosphorylating vir G. Now protein G is transcription factor which means once it is activated it transcribes remaining genes of vir region i.e. vir B, vir C, vir D and vir E.
  •   The first vir gene to be transcribed is vir C, which makes a complex with right T-DNA border.
  •   Second gene in the line is vir D which act as endonuclease. It recognizes the right T-DNA border + protein C complex and it will digest or form a nick in that region.
  •   Third event is formation multiple copies of vir E gene. Now this multiple copies of protein E would bind to the nicked portion of T-DNA and escorts it from bacteria to plant.
  •   But wait, how would it take T-DNA from bacteria to plant? Is there any channel or bridge between both? This problem is solved by vir B gene which provides bridge between the bacteria and plant and T-DNA is transferred through this.
  •   Following the transfer of T-DNA to plant, it gets inserted into the chromosome of plant. Now remember we just saw that T-DNA has auxin production, cytokinin production and opine synthesis genes? So these genes will now start getting expressed. When auxin and cytokinin genes are expressed, it causes uncontrolled growth of plant cell resulting into tumor or Crown Gall disease.
  •   What about opine synthesis gene? When it is expressed, it secretes opine into the soil which attracts the soil Agrobacterium and they will utilize this opine as their nutrient source.

 

Wonderful mechanism, isn’t it? Now my favorite part!! How to remember functions of these genes? What I do is, I correlated their function with what a gene is called. Like,

A = Autophophorylation

G = Gene transcription

C = Complex formation with T-DNA

D = Digestion

E = Escorting T-DNA

B = Bridge formation

 
For more explanation watch this video.