Haematopoiesis Flashcards
define haematopoiesis
process of blood cell formation
What embryonic structure is the main site of haematopoiesis in the first few weeks of gestation?
yolk sac
What is the aorta-gonads-mesonephros region?
It is the first site within the embryo where definitive hematopoiesis occurs. This means that it is the initial location where hematopoietic stem cells capable of long-term blood cell production are formed. These HSCs then migrate to haematopoietic organs e.g. the liver, spleen and bone marrow.
Further notes:
The AGM region is derived from the mesoderm layer and includes the dorsal aorta, genital ridges, and mesonephros. It is situated between the notochord and the somatic mesoderm, extending from the umbilicus to the anterior limb bud of the embryo. [Diagram]
State the important sites of haematopoiesis in the foetus at:
(a) 0 - 2 months
(b) 2 - 7 months
(c) 5 - 9 months
(a) 0 - 2 months: yolk sac
(b) 2 - 7 months: liver, spleen
(c) 5 - 9 months: bone marrow
Haematopoiesis in the bone marrow is called ____(a)____ haematopoiesis, whereas haematopoiesis in areas other than the bone marrow is called ____(b)____ haematopoiesis.
When may (b) occur and what may it result in?
(a) medullary
(b) extramedullary
Extramedullary haematopoiesis may occur in the even that the bone marrow cannot meet the physiologic needs of the tissues. This can lead to hepatomegaly or splenomegaly.
hematopoiesis is dependent on three important components
(a) progenitor cells
(b) bone marrow stroma
(c) hematopoietic growth factors
discuss hematopoietic stem cells and hematopoietic progenitor cells
Hematopoietic stem cells are pluripotent stem cells that can give rise to separate cell lineages. They posses long-term self-renewal capacity, meaning they can divided and produce more stem cells over a lifetime.
Hematopoietic progenitor cells are derived from hematopoietic stem cells and are more restricted in their differentiation potential. They can give rise to specific types of blood cells but lack extensive-self renewal capacity.
Further notes:
The earliest detectable mixed myeloid precursor which gives rise to granulocytes, erythrocytes, monocytes and megakaryocytes is termed CFU (colony-forming unit) - GEMM.
A mixed-myeloid precursor refers to a type of hematopoietic progenitor cell that has the potential to differentiate into various myeloid lineages. These cells are part of the broader category of hematopoietic stem and progenitor cells and are crucial for the formation of different types of myeloid cells, such as: granulocytes, monocytes, erythrocytes and megakaryocytes. [The term myeloid refers to a category of blood cells that originate from the bone marrow.]
(a) Name four cells found in bone marrow stroma.
(b) State the function of these cells.
(a) adipocytes, fibroblasts, endothelial cells, macrophages
(b) They secrete extracellular molecules such as collagen, glycoproteins and glycosaminoglycans to form an extracelluar matrix. These stromal cells also secrete various growth factors necessary for stem cell survival.
What are hematopoietic growth factors?
These are glycoprotein hormones that regulate the proliferation and differentiation of haematopoietic progenitor cells and the function of mature blood cells.
How do haematopoietic growth factors act?
They may act locally at the site where they are produced by cell-cell contact or circulate in plasma. They also bind to the extracellular matrix to from niches to which stem and progenitor cells adhere.
Further notes:
Here’s how HGFs interact with the ECM to form niches for stem and progenitor cells:
(1) Binding to ECM: HGFs can bind to components of the ECM, such as fibronectin, collagen, and proteoglycans. This binding helps localize the growth factors within specific areas of the bone marrow.
(2) Formation of niches: These localized areas, provide a supportive environment for hematopoietic stem cells and progenitor cells. The ECM, along with HGFs, creates a microenvironment that maintains the stem cells in a quiescent state or promotes their proliferation and differentiation as needed.
(3) Adhesion of stem and progenitor cells: The ECM and HGFs facilitate the adhesion of HSCs and progenitor cells to the niche. This adhesion is crucial for the proper functioning and regulation of these cells, ensuring they remain in the bone marrow and receive the necessary signals for their development.
(4) Regulation of cell behavior: By binding to the ECM, HGFs can modulate the behavior of HSCs and progenitor cells, influencing their survival, proliferation and differentiation. This interaction ensures a balanced production of different blood cell types.
What effects do haematopoietic growth factors have on cells?
They can cause cell proliferation, stimulate differentiation and maturation, prevent apoptosis, and affect the function of mature cells.
Name some key haematopoietic growth factors.
erythropoietin, granulocytes colony-stimulating factor, thrombopoietin
Where are erythropoietin and thrombopoietin primarily produced?
Erythropoietin is primarily synthesized in the kidneys; thrombopoietin is primarily synthesized in the liver.
What are general characteristics of myeloid and lymphoid growth factors?
✓ They are glycoproteins that act at very low concentrations.
✓ They act hierachically.
✓ Usually produced by many cell types.
✓ Usually affect more than one lineage.
✓ Usually active on stem/progenitor cells and on non-functional end cells.
✓ Usually show synergistic or additive interactions with other growth factors.
✓ Often act on the neoplastic equivalent of a normal cell.
✓ Multiple actions: proliferation, differentiation, maturation, functional activation, prevention of apoptosis of progenitor cells.
