L08 - Stem Cells

Question 1

What are the two types of self-renewal?

How do they differ?

Answer 1

• Expansion is the symmetrical form of self-renewal in which the stem cell gives rise to two daughter cells that are identical to the parent stem cell
• Maintenance is the asymmetrical form of self-renewal in which the stem cell gives rise to one daughter cell that is identical to the parent stem cell, and another daughter cell which is slightly different from the original stem cell, forcing it to take on a particular lineage
• Expansion only occurs in early embryonic development. After that time, the stem cells take on the asymmetrical ‘maintenance’ form of self-renewal

Question 2

What is the function of quiescent stem cells?

Answer 2

• Quiescent stem cells provide a tissue with a reservoir of normal stem cells to act as a failsafe should a tissue become damaged
• They are able to exit quiescence and undergo asymmetric ‘maintenance’ self-renewal in response to an external damage signal

Question 3

What is stem cell potency?

Answer 3

Stem cell potency is the measure of the number of different differentiated cells to which a stem cell can give rise

Question 4

Define stem cell niche.

Answer 4

Stem cell niche refers to the tissue in which a stem cell resides

Question 5

What is the functional difference between embryonic stem cells and adult stem cells?

Answer 5

• Embryonic stem cells give rise to the embryo proper

- Adult stem cells maintain tissues throughout life

Question 6

Until which stage in embyrological devleopment are all of the stem cells in the embryo identical?

How do the totipotent stem cells change with their first differentiation?

Answer 6

• The first differentiation begins at the morula stage (after the 8 cell stage)
• At this point, totipotent stem cells become pluripotent stem cells. This means that they can give rise to every tissue of the embryo proper (endoderm, mesoderm and ectoderm) , but cannot give rise to extraembryonic tissue (i.e. the placenta)

Question 7

Which pluripotent stem cells from embryological development remain in the body for life?

Answer 7

• Only the pluripotent stem cells that migrate to the gonads to produce gametes remain in the body for life
• The rest of the pluripotent stem cells continue to differentiate

Question 8

List 3 genes that are involved in the balance of pluripotency factors in stem cells.

Answer 8

1 - Oct4

2 - Sox2

3 - Nanog

Question 9

What controls the migration of epiblast cells?

Answer 9

• Migration & specification controlled by FGF8 (synthesised by primitive streak cells)
• Controls cell movement by downregulating E-cadherin & cell specification into mesoderm by regulating BRACHYURY (T) expression

Question 10

What is the function of the oct4 / sox2 genes?

Answer 10

• The oct4 and sox2 genes encode transcription factors
• A specific balance of oct4 and sox2 can force a cell down a specific cell lineage programme (endoderm, mesoderm or ectoderm)

Question 11

List 3 problems with using embryonic stem cells in regenerative medicine.

Answer 11

1 - Production of the pure required cell type in sufficient numbers

2 - Delivery of the cells and proper incorporation (e.g. in the heart, overcoming existing scarring)

3 - Immune rejection (as the stem cells are allogeneic)

Question 12

Describe the process of somatic cell nuclear transfer (SCNT).

What is the advantage of using SCNT for stem cell therapy?

Answer 12

• Transfer of the nucleus of a somatic cell into an oocyte, and then triggering cell division
• The inner cell mass is then removed at the blastocyst stage and cultured to make specific tissues
• The advantage of SCNT is that the stem cells produced won’t be immune rejected by the patient

Question 13

What are iPS cells?

How are they produced?

Answer 13

• iPS cells are induced pluripotent stem cells
• They are embryonic stem cell-like cells that are produced by the transfection of fibroblasts with a combination of pluripotency-inducing transcription factors
• The process involves reversing the differentiation process from a fully differentiated cell, through all stages of potency, back to a pluripotent stem cell. This process is known as dedifferentiation

Question 14

Define transdifferentiation.

Answer 14

Transdifferentiation is the conversion of one differentiated cell type directly to another, without forcing it backwards into an earlier stage of potency

Question 15

Why is vitamin C useful for reprogramming cell lineages?

Answer 15

• One of the barriers of cell reprogramming is cell senescence, which accounts for the slow kinetics and low efficiency of the reprogramming process
• Vitamin C prevents cell senescence, so makes the reprogramming process faster