Haematopoeisis Flashcards
There are ____________ blood cells produced everyday
260 billion
Why is haematopoeisis a dynamic process?
There is continuous turnover of cells
It has to respond to acute stimuli i.e. infection and bleeding
Blood cells make up __% of the blood and plasma makes up __%
45%
55%
What are the percentages of RBC, leukocytes and thrombocytes?
44% RBC
1% Leukocytes
What are HSC’s?
Haemopoeitic Stem Cells
What are LT-HSC’s?
Long Term Haematopoeitic Stem Cells
Can supply an irradiated mouse for a long time
Are able to self renew and maintain the stem cell pool
What are ST-HSC’s?
Short Term Haematopoeitic Stem Cells
Can supply an irradiated mouse for only 6 months
They are stimulated to differentiate to become blood cells
A ST-HSC can differentiate in to 2 lineages. What are they?
The Myeloid lineage, ST-HSC -> Common Myeloid Progenitor
The Lymphoid lineage, ST-HSC -> Common Lymphoid Progenitor
Where does Haematopoeisis occur in the foetus?
0-2 months in the yolk sac
2-7 months in the liver and spleen
5-9 months in the bone marrow
Where does Haematopoeisis occur in the adult?
Vertebrae Ribs Sternum Skull Pelvis Proximal ends of the femur
Primitive Haematopoesis occurs ____________________________
Outside of the bone marrow during earl foetal development
Definitive Haematopoeisis occurs ________________________
Inside the bone marrow from 5 months (In-utero) and through adult life
HSC’s are defined as ________ stem cells.
Pluripotent
HSC’s undergo divisions to:
- Increase or maintain their numbers (Self-renewal)
- Generate a heterogeneous pool of progenitors
- Sustain haematopoeisis over the lifetime of the individual
Stem cells reside in the ________ in a ____ oxygen environment called a niche where they remain ________ until stimulated
Bone Marrow
Low
Inactive
What happens when a stem cell is stimulated?
They move towards the vascular niche to differentiate
_________ and ___ cells produce several factors that support HSC cells including ________
Osteoblasts and SNO cells
Thrombopoietin
Explain the process of RBC differentiation
- Commited cell (Pro-erythroblast) undergoes ribosome synthesis
- Haemoglobin is produced
- Nucleus and organelles are ejected
- Moves into circulation and becomes a mature erythrocyte
How are platelets produced?
- Commited cell develops (Pro-megakaryocyte)
- Undergoes endomitosis (Nucleus divides over and over but cell doesn’t divide)
- Cytoplasmic extensions called proplatelets extend into the blood vessel
- Flow of blood dislodges proplatelets and they become platelets
Outline the EPO/TPO signalling process
- Erythropoetin or Thrombopoetin bind to either an EPO or TPO receptor respectively
- Receptor dimerises, bringing molecules on their tails together
- A set of reactions is set off which causes specific genesto be expressed
What transcription factors are needed for RBC formation?
GATA 1 FOG 1 c-myb p300 Klf1
What transcription factors are needed for Megakaryote formation?
GATA 1 FOG 1 GABP α RUNX1 FLI1
What 2 genes are essential for Haematopoeisis?
EPOR
JAK2
What are LICs?
Leukaemia Initiating Cells
Small population of cells responsible for tumour maintainence
They are CD34+ and CD38-
LICs, particulary those is a ________ state, are thought to be resistant to _____________________ therapies and contribute to disease relapse
Quiescent
Chemotherapy and Targeted therapies
