Lecture 6 - The stem cell niche

Question 1

Describe the potency of stem cells initially in the embryo?

Answer 1

Totipotent

Question 2

What cells are produced from mesenchymal stem cells?

Answer 2

• bone cells (osteoblasts)
• cartilage cells (chondrocytes)
• fat cells (adipocytes)

Question 3

What cells are produced from haematopoetic stem cells?

Answer 3

• blood stem cells
• red blood cells
• platelets
• white blood stem cells

Question 4

What cells are produced from satellite stem cells?

Answer 4

muscle

Question 5

What cells are produced from germ cells?

Answer 5

• oocytes
• sperm

Question 6

What is the name given to the special environments where adult stem cells are found?

Answer 6

niches

Question 7

Why do we need stem cells?

Answer 7

maintenance

Question 8

How long do RBC live for?

Answer 8

4 months

Question 9

How long do white blood cells live for?

Answer 9

> a year

Question 10

How long do skin cells live for?

Answer 10

2-3 weeks

Question 11

How long do colon cells live for?

Answer 11

4 days

Question 12

How long do sperm cells live for?

Answer 12

3 days

Question 13

How long do brain cells last?

Answer 13

can live for an entire lifetime

Question 14

What process allows stem cell to carry out maintenance?

Answer 14

mitosis

Question 15

How is stem cell division different from normal mitosis?

Answer 15

creates a daughter cell and keeps a stem cell

Question 16

What is the advantage of stem cell division compared to normal mitosis?

Answer 16

maintains the stem cell population

Question 17

What is the name of the stage by which the daughter cell, created through stem cell division, differentiates to create many cells?

Answer 17

transit amplifying stage

Question 18

What is population asymmetry?

Answer 18

3 different types of division to ensure that division rates are in balance that keep the stem cell population constant

Question 19

What are the 3 types of cell division which maintains population asymmetry?

Answer 19

1. stem cell proliferates into 2 stem cells
2. stem cell proliferates into 2 differentiated cells
3. stem cell proliferates into one of each

Question 20

What are the 3 main layers of the skin?

Answer 20

epidermis, dermis & subcutis

Question 21

What can be found in skin?

Answer 21

• hair follicles
• sebaceous glands
• sweat glands

Question 22

What is the epidermis made up of?

Answer 22

keratinocytes

Question 23

What does the dermis contain?

Answer 23

fibroblasts & blood vessels

Question 24

What stimulates keratinocyte proliferation?

Answer 24

signals from the dermis & basement membrane

Question 25

What type of stem cells (that can proliferate) can be found in the stem cell niche that is the basal layer?

Answer 25

basal keratinocytes

Question 26

What happens to the daughter cells (basal keratinocytes) when they proliferate?

Answer 26

pushed progressively to the skin surface where they die

Question 27

What provides the skin with strength?

Answer 27

high levels of fibrous protein keratin

Question 28

What happens to cells as they move towards the surface?

Answer 28

produce different keratin

Question 29

Where are dead keratinocytes found?

Answer 29

on the outer layer of the skin

Question 30

What separates & holds the dermis and epidermis together?

Answer 30

extracellular matrix

Question 31

What signals come from the dermis that impacts differentiation?

Answer 31

Wnt

Question 32

How does Wnt (from dermis) impact differentiation?

Answer 32

Wnt inhibits differentiation, which maintains stem cell population

Question 33

How does Integrins maintain stem cell population?

Answer 33

Integrins hold cells to the basement membrane. This adhesion allows for the maintenance of stem cell population.

Question 34

How do notch signals influence the maintenance of stem cell population?

Answer 34

Notch signals in maturing keratinocytes inhibit integrins. This stops adhesion between cells and the basement membrane. As a result, this causes a reduction in stem cell populations.

Question 35

What is the protein that can inhibit Notch signal activity?

Answer 35

EGF (epidermal growth factor)

Question 36

What is the stem cell niche located in the hair follicle?

Answer 36

the bulge

Question 37

What is the purpose of the bulge found in the hair follicle?

Answer 37

Provide the cells that form the follicle

Question 38

What can bulge cells contribute when skin is badly damaged?

Answer 38

bulge cells can also contribute to epidermis & sebaceous glands, which can aid in the replacement of damaged skin.

Question 39

What occurs as a whole to stem cell niches after injury, when larger areas of restoration are needed?

Answer 39

different stem cell niches may be able to provide cells

Question 40

What occurs in patients with Junctional epidermolysis bullosa (JEB)?

Answer 40

the adhesion between dermis and epidermis is impaired, due to mutation in adhesion genes - LAMB3

Question 41

What can be used to replace skin in burn patients?

Answer 41

Skin epidermis (basal keratinocytes) that have been cultured

Question 42

What can be used to reintroduce DNA into cells, when skin epidermis have been cultured from JEB patients?

Answer 42

inactivated viruses (viral vectors)

Question 43

Why does our gut lining need to be continuously replenished?

Answer 43

Due to the harsh environment created due to our gut content

Question 44

What are the different types of cells found in the small intestine?

Answer 44

- enterocyte - goblet cells - enteroendocrine cells - paneth cells - stem cells - submucosal cells

Question 45

What process are enterocyte cells involved in?

Answer 45

absorption

Question 46

What is the function of goblet cells?

Answer 46

Secrete mucus

Question 47

What is the function of enteroendocrine cells?

Answer 47

secrete peptide hormones

Question 48

What is the function of Paneth cells?

Answer 48

secrete anti-microbial peptides

Question 49

What is the function of submucosal cells?

Answer 49

help maintain the stem cells

Question 50

Where are stem cells located?

Answer 50

base of the crypt

Question 51

How many cells does each crypt create in a mouse?

Answer 51

12 cells per hour

Question 52

How many cells is a crypt made up of?

Answer 52

250 cells

Question 53

What hormone does slow-dividing stem cells express?

Answer 53

Bim1

Question 54

What hormone does fast-dividing stem cells express?

Answer 54

Lgr5

Question 55

What are Bim1 & Lgr5 markers for?

Answer 55

Stem cells

Question 56

How do we know that Lgr5 positive cells are stem cells?

Answer 56

Lineage tracing allows us to determine the fate of a cell

Question 57

What can be made that causes single cells to express a marker?

Answer 57

Transgenes

Question 58

How can embryonic stem cells be grown?

Answer 58

they can be isolated from the epiblast & grown in cell culture

Question 59

How is the embryonic stem cells kept in a pluripotent state?

Answer 59

They are kept in specially defined conditions, with BMP & LIF present

Question 60

What occurs if BMP & LIF signals were removed from the embryonic stem cells?

Answer 60

this would lead to differentiation into different cell types - each cell type requiring a specific set of conditions.

Question 61

What is the difference between human and mouse ES cells?

Answer 61

human - pluripotent & require FGF + activin mouse - totipotent & require different treatment (BMP & LIF)

Question 62

What are the assays (tests) for pluripotency?

Answer 62

Expression of epiblast markers (transcription factors): - Nanog - Oct4 - Sox2 - Klf4

Question 63

How are chimeras made?

Answer 63

created when ES cells are mixed in with a normal embryo & the ES cells contribute to different tissues in the adult

Question 64

What are teratomas?

Answer 64

benign tumours that contain differentiated tissues

Question 65

What occurs if we activate epiblast marker expression in differentiated cells?

Answer 65

the cells dedifferentiate and become stem cells

Question 66

What factors are used to convert differentiated cells into IPS cells (induced pluripotent stem cells)?

Answer 66

Yamanaka factors

Question 67

What is the advantage of using Yamanaka factors to create IPS cells instead of ES cells?

Answer 67

Ethically less complex - ES cells can be quite difficult to obtain