Tissue/adult stem cells

Question 1

What is an adult stem cell?

Answer 1

A stem cell present in adult tissues/organs that retains the characteristics of stem cells i.e. self-renewal and potency, except that adult stem cells are usually unipotent or multipotent

Question 2

What is cellular homeostasis? (2)

Answer 2

• The constant/periodic generation of new cells to replace old, damaged and dying cells or the addition of new cells as needed
• Adult stem cells fulfil this role through regeneration/replacement

Question 3

How do stem cells divide asymmetrically? (3)

Answer 3

• One daughter cell is another adult stem cell
• Other daughter cell is a transit-amplifying (progenitor) cell which rapidly proliferates and they differentiate
• Differentiated cells go on to repair damage

Question 4

What is a stem cell niche?

Answer 4

A specialised, tissue-specific microenvironment that regulates adult stem cells

Question 5

What are the 2 main components of a stem cell niche?

Answer 5

• Physical
• Chemical

Question 6

What are the physical aspects of a stem cell niche? (2)

Answer 6

• Cell adhesion
• Extra-cellular matrix

Question 7

What are the chemical aspects of a stem cell niche? (2)

Answer 7

• Secreted proteins (signalling molecules)
• Metabolic molecules (Ca2+, ROS)

Question 8

What intracellular mechanisms regulate adult stem cells? (3)

Answer 8

• Epigenetic regulation
• Transcriptional regulation
• Cytoplasmic determinants

Question 9

What is epigenetic regulation of stem cells?

Answer 9

Histone modifications and methylation influence the expression of stem cell genes

Question 10

What is transcriptional regulation of stem cells?

Answer 10

Networks of transcription factors regulate stem cell quiescence, proliferation, differentiation and self-renewal

Question 11

What is quiescence?

Answer 11

Inactivity/dormancy

Question 12

What is cytoplasmic regulation of stem cells?

Answer 12

Asymmetric distribution of proteins govern the mode of cell division

Question 13

What is the stem cell niche for the germline stem cells in drosophila?

Answer 13

The germarium within the ovarioles

Question 14

How does germline stem cell differentiation occur in drosophila? (3)

Answer 14

• 2 germline stem cells in each germarium which are tightly associated with cap cells via E-cadherin adherens junctions
• Germline stem cells divide asymmetrically forming one self-copy and one cystoblast cell
• Cystoblast cell does 4 rounds of cell division and 1 out of the 16 cells becomes the oocyte

Question 15

How is the germline stem cell maintained in drosophila? (3)

Answer 15

• Cap cells secrete TGFβ which binds to receptors on the germline stem cells and activates BMP signalling
• bam gene is suppressed which is required for differentiation
• Close association of cap cells and germline stem cells via adherens junctions required

Question 16

How does germline stem cell differentiation occur in drosophila? (2)

Answer 16

• Asymmetric cell division means one of the daughter cells moves away from the cap cells and TGFβ secretion
• No BMP signalling occurs in the cell so bam is no longer suppressed so differentiation can occur

Question 17

What is the equivalent of BMP signalling in drosophila?

Answer 17

dpp

Question 18

What happens to drosophila germline stem cells when you lose BMP signalling/overexpress bam?

Answer 18

Differentiation

Question 19

What happens to drosophila germline stem cells when you overexpress BMP signalling/lose bam?

Answer 19

Germline tumours (too much stem cell self-renewal)

Question 20

What are satellite cells?

Answer 20

Skeletal muscle stem cells

Question 21

Where is the stem cell niche for skeletal muscle stem cells?

Answer 21

Between muscle fibre and basal lamina

Question 22

How do skeletal muscle stem cells respond to damage? (4)

Answer 22

• Reside in G0
• Damage causes them to activate and enter the cell cycle
• Generate progenitor cells which differentiate and repair damage
• Stem cell pool is maintained

Question 23

How are skeletal muscle stem cells maintained? (4)

Answer 23

• Apical-basal asymmetric cell division
• Par1 accumulates on the basal side and suppresses par3 which accumulates on the apical side
• Par3 in the apical cell activates p38 MAPK which induces myoD transcription
• MyoD drives differentiation so the apical cell becomes muscle and the basal cell is maintained as a stem cell

Question 24

What is the importance of ECM/basal lamina remodelling in the skeletal muscle stem cell niche? (3)

Answer 24

• Satellite cells secrete MMP2/9 in response to damage which digests the ECM
• Satellite cells start synthesising laminin α1 instead of α2
• Laminin α1 is required for asymmetric distribution of par proteins

Question 25

What are the therapeutic advantages of adult stem cells? (5)

Answer 25

• Already specialised so induction of differentiation into specific cells is easier
• Plasticity
• No immune rejection in autologous transplant
• No risk of teratomas (unlike embryonic stem cells)
• No ethical controversy

Question 26

What are the therapeutic disadvantages of adult stem cells? (4)

Answer 26

• Limited quantity
• Limited lifespan in culture
• If isolated from aged individuals they may carry genetic damage due to ageing
• Potential of rejection if donor cells are from another individual