Week 8 Flashcards
(16 cards)
1
Q
What germ layer gives rise to blood cells?
A
- Blood cells are derived from the lateral plate mesoderm, specifically the splanchnic
2
Q
What are the two stages of haematopoiesis?
A
- Primitive: embryonic
2. Definitive: adult
3
Q
Describe primitive haematopoiesis:
A
- Transient phase that provides the embryo with its first blood cells
- Occurs in the yolk sac (for the first 6 weeks almost all RBCs are produced in the yolk sac)
- All blood cells are produced except lymphocytes and erythroblasts (early red blood cells)
- Blood islands are formed from the mesenchymal cells from the splanchnic lateral mesoderm, these mesenchymal cells form hemangioblasts under the influence of BMP
- The central cells of the blood islands form blood cells and the peripheral cells form the endothelial cells that line blood vessels
- The intraembryonic vitelline vessels link the yolk sac to the embryo which allows the embryonic erythrocytes to circulate
4
Q
What is the difference between embryonic and adult erythrocytes?
A
- Embryonic erythrocytes are large and nucleated
- They express embryonic globin genes
5
Q
What is the adult phase of haemopoiesis?
A
- Provides the foetus and embryo with vrious cell types that make up blood and generates the haemopoietic stem cells
- Occurs in the aorta-gonad-mesonephros system (AGM)
- Ultimately it occurs in the liver, placenta, spleen and bone marrow
- Haemopoietic stem cells (HSCs) are derived from the splanchnic mesoderm surrounding the dorsal aorta (the AGM region)
- By week 5-6 haemopoiesis begins in the fetal liver as the HSCs move from the AGM to the liver as well as the spleen
- By about 6 months of development HSCs have migrated to the bone marrow and there is increased blood cell production from the bone marrow
6
Q
What are HSCs?
A
- Haematopoietic stem cells are multipotent stem cells
- They can give rise to all blood cell types
- HSCs can divide to form more HSCs or committed progenitor cells including common myeloid progenitor, common lymphoid progenitors, megakaryocyte/erythroid progenitors and granulocyte/monocyte progenitors
7
Q
What is the haemopoitic stem cell niche?
A
- HSCs have a stem cell niche where they are in contact with marrow stromal cells and endosteal osteoblasts of bone
- The development path taken by HSCs depends on factors e.g. colony stimulating factors (made by stromal cells)
- The HSC niche responds to environmental changes
- An example of a colony stimulating factor is EPO which is a colony stimulating factor that increases erythroid progenitors and thus RBC count
8
Q
What is blood?
A
- A loose connective tissue
- Made up mostly of a liquid ECM (plasma) 55%
- with cellular components that include erythrocytes (45%), leukocytes (<1%) and platelets
9
Q
What are the components of plasma?
A
- 90% water
- 7% plasma proteins including albumin (maintains osmotic pressure of blood), globulins (antibodies) and fibrinogen (necessary for formation of fibrin for the final step of coagulation
- 2.1% amino acids, hormones, vitamins and lipoproteins
- 0.9% inorganic salts
10
Q
Describe the pathway of differentiation from multipotent HSCs:
A
- After division one cell will remain a multi-potent HSC and the other will form a committed progenitor, which will either be a: lymphoid or myeloid progenitor
- Lymphoid progenitors form T cells, B cells and NK cells
- Myeloid progenitors form either granulocyte/macrophage progenitors (macrophages, dendritic cells, granulocytes) or megakaryocyte/erythroid progenitors (megakaryotes-platelets or erythrocytes)
11
Q
What are the 2 processes by which blood vessels develop?
A
- Vasculogenesis:
2. Angiogenesis
12
Q
Describe Vasculogenesis:
A
- First seen in the blood islands of the yolk sac
- Vasculogenesis also occurs within each organ as it develops (intraembryonic vasculogenesis)
- During intraembryonic vasculogenesis it occurs in mesodermal cells surrounding the organs that then burrow into the organ
- Vasculogenesis is regulated by 3 factors:
1. Fibroblast growth factor 2 - needed for generation of haemangioblasts from mesodermal cells
2. Vascular endothelial growth factor - promotes proliferation and differentiation of angioblasts to form endothelial cell tubes
- VEGF knockouts lack blood vessels in the yolk sac and die
3. Angiopoietins: - mediate interactions between endothelial cells and pericytes (the smooth muscle like cells)
- Angiopoietin KO mice have malformed blood vessels hat are deficient in smooth muscle
13
Q
Describe angiogenesis:
A
- After the initial phase of vasculogenesis, angiogenesis begins
- By this process the primary capillary networks are remodelled and veins and arteries are made
- Angiogenesis is basically the sprouting and extension of new vessels from existing vessels
- Angiogenesis involves:
1. Loosening of contacts between endothelial cells
2. Breakdown of ECM at specific points
3. Exposed endothelial cells proliferate and sprout from these regions
4. The loosening of cell-cell contacts may also allow the fusion of capillaries to form wider vessels such as arteries and veins - PDGF is necessary for recruitment of pericytes that contribute to the wall of the new vessel (PDGF-receptor is expressed on pericytes/SMCs)
14
Q
What determines if an artery or vein will develop?
A
- Two types of endothelial cells exist which give rise to either arteries or veins
1. Endothelial cells that express Ephrin-B2-LIGAND: form arteries
2. Endothelial cells that express Ephrin-B2-RECEPTOR: form veins
15
Q
How do nerves influence the development of arteries?
A
- Blood vessels follow peripheral nerves
- Nerves secrete VEGF needed for artery formation (vasculogenesis)
- Arteries are secrete glial cell line derived nerve growth factor which allows the nerves to grow alongside the vessel
16
Q
How do lymphatic vesicles develop?
A
- Lymphatic vesicles are initiated from a subset of endothelial cells that sprout from the cardinal vein
- The transcription factor Prox-1 is an early marker for commitment to the lymphatic lineage
- VEGF-C is critical for the formation of lymphatic vesicles
