Stem Cell Hierarchy

Question 1

What are the three key parts in the job description of a stem cell?

Answer 1

• Be versatile: give rise to the full range of differentiated cells
• Be productive: replace in excess of 10^11 blood cells per day
• Retain stemness: output required for several decades

Question 2

What are the five major characteristics of the haematopoietic stem cell?

Answer 2

1. support haematopoiesis through life
2. can be enriched phenotypically (but not fully characterised)
3. give rise to differentiated progeny whilst themselves remained undifferentiated
4. Rare
5. Usually quiescent

Question 3

Output must be sustainable for long term haematopoiesis - what does this depend on and how can we find out if occurs?

Answer 3

• Depends on continued presence of cells which are capable of self renewal
• Sustained haematopoiesis can be demonstrated experimentally through serial transplantation

Question 4

How do stem cells achieve the dual task of self-renewal and generation of differentiated cells?

Answer 4

Through their ability to choose between symmetric and asymmetric division

Question 5

What are asymmetric and symmetric division in the context of haematopoietic stem cells?

Answer 5

• Asymmetric: each stem cell generates one daughter stem cell and one daughter destined to differentiate
• Symmetric: each stem cell can divide symmetrically to generate either two daughter stem cells or two differentiated cells

Question 6

What are the benefits of HSCs being able to maintain a dormant, quiescent state?

Answer 6

• Prevents exhaustion

- Protects the genome

Question 7

What are the four main methods that have established quiescence in HSCs?

Answer 7

• Gene marking studies
• BrdU labelling
• Telomere length measurement
• Subset transplantation

Question 8

What are the estimated lifespan, replication frequency and divisions per life time of a HSC in humans?

Answer 8

• Lifespan = 90 years
• Replication freq = once every 45 weeks
• Divisions per lifetime = 104

Question 9

How would we define a cancer stem cell?

Answer 9

• perpetuates the tumour
• Gives rise to the range of cells found in the tumour (including clonogenic cells and non-proliferating progeny)
• Doesn’t always have a defined phenotype
• Not always rare or quiescent