Tissue Homeostasis

Question 1

What are stem cells and why are they needed in adults?

Answer 1

1. Cells that can renew tissues that slowly loose cells
2. slow dividing
3. imortal
4. protection against accumulation of mutations

Question 2

What are examples of why stem cells are needed?

Answer 2

• Blood cells: adult RBC die every 100 days and dont have a nucleus so can’t proliferate
• Gut cells: epithelium (lining of the gut) renewed
• Skin surface cells: renewed often and dont have a nucleus

Question 3

How is asymetrical division generated?

Answer 3

1. Environment (neighbouring cells/ECM/GF)
2. inside cell’s localised compartment

Question 4

What were the effects of radiation on the haematopoetic system?

Answer 4

Stem cells discovered after WW2 hiroshima bomb. Increased radiation= death but could be saved by bone marrow transplant

Question 5

What did Till and McCulloh discover and how?

Answer 5

Found that transplanted bone marrow could save radiated mice.
Radiating bone marrow= death
Transplanting radiated bone marrow= death
Showed that mice spleen came from 1 bone marrow cell bc found colonies all had the same mutation from the radiated bone cell.

Question 6

Do plants have stem cells?

Answer 6

Yes? they have apical meristems that seem to give rise to different cells.

Question 7

What stem cell therapies are there?

Answer 7

Bone marrow transplants after irradiation are used in leukemia therapy

Question 8

What is the niche for in Drosophilia GSC cells?

germline stem cells

Answer 8

Niche=stem cell environment that provides stuff needed to maintain stem cells
Cap cells are the niche. They provide signals that turn Bam off (keep it as stem cells)

Question 9

What phenotype do BAM mutants have?

Answer 9

Loss of function mutants have too many germ cells. Means that Bam on triggers GSC’s to differentiate

Question 10

How do spectrosomes create asymetrical division?

Answer 10

The cell that inherets the spectrosome when it divides remains the GSC. GSC anchored to niche by adheren. Spectrosome made of spectrin (binds actin)

GSC’s are linked to cap cells (their niche) by spectrosomes because creates orientated division of the cells away from the cap cells, therefore the new cells have Bam ON opposed to the ones that stay near the cap cells where Bam is OFF

Question 11

What is mamillian hair follicle an example of?

Answer 11

Mamillian stem cells that undergo asymetric division. The cells that remain anchored are the self renewable ones.

Question 12

What cell types compose the gut epithelium?

Answer 12

Enterocytes: absorb nutrients (villi)
Goblet cells: secrete mucus (villi)
Enteroendocrine cell: secretes hormones (villi)
Paneth cell: mediates microbial immunity (base of crypt)
CBC cells: express Lgr5 aka stem cell (base of crypt)

crypt base columnar= CBC

Question 13

How were gut stem cells (Lgr5+) discovered?

Answer 13

First GFP was added to the promoter region of Lgr5. Then the promoter was engineered to express CreET2, which is only active when tamoxifen. When CreET2 is on it turns on LacZ (blue) in the Lgr5 cells. So cells that express Lgr5 would be blue/green and their descendents were blue. The blue/green ones always stayed in the crypt proving CBC were stem cells

Question 14

How was it proven that Paneth cells were the niche for CBC?

Answer 14

CBC makes gut organoids in vitro, but only really grow with paneth cells. Paneth cells can be replaced by Wnt3, prooving Paneth cells are the niche for CBC.

Question 15

Do CBC divide asymetrically or symetrically? How was this determined?

Answer 15

They divide symetrically. Each CBC was tagged with a fluoresence protein, and after a while each crypt was one color- prooves they divide symetrically. Follows a neutral drift model

Why? In a limited space its likely that one of the 5-7 cbc dominated eventually over the rest of them- which fits mathmatically. There is another posibility that the crypt is all one stem cell but this isnt likely

Question 16

What organs regenerate well?

Answer 16

Gut, skin, haemopoetic system

Question 17

What organs regenerate slowly?

Answer 17

Muscle, liver

Question 18

What organs do not regenerate well?

Answer 18

Lens, brain, heart

Question 19

How are TA cells involved in regeneration?

TA= transient amplifying

Answer 19

They are a back up. When Lgr5+ cells are radiated they die (bc no lacz label) but still Lgr5+ are found in crypt and villus (w/o lacZ). Implies TA cells were turned into stem cells.

Question 20

Regarding gut regeneration

What did the assisted regeneration experiement show?

Answer 20

Healthy gut organoids could be transplanted and save a dying mouse. Shows that Wnt3 essential for growing organoid and also that they have healing properties.

Question 21

What are the different layers of the epidermis?

Answer 21

1. Cornified
2. Suprabasal
3. Basal
4. Dermis

Question 22

How does the epidermis regenerate cells?

Answer 22

Stem cells are in the basal layer. They proliferate and give rise to suprabasal cells. Suprabasal cells make their way up and lay down a protein matrix, then ennucleate themselves and die. Doing this creates a barrier against pathogens or stressors

Question 23

How do scientists grow skin?

Answer 23

Scientists can propigate holoclones (stem cells) which can be applied to burn victims and give them new skin

Epidermal cells give rise to 3 colonies in vitro: holoclone, merclone, and pariclone of which only holoclone lived ‘forever’

Question 24

What are satellite cells?

Answer 24

Long thin multinucleated cells that are Muscle stem cells, used to regenerate muscles and are located on the edge of muscle fibres

Question 25

How does muscle stem cell regeneration work?

Answer 25

Satellite cells express Pax3 and give rise to contractile fibres. Pax3 can be isolated and transplanted in a mouse that lacks dystopian, and generate dystopian

Question 26

In regard to regeneration

What is important about Hydra?

Answer 26

Hydra can regenerate into 2 individuals after being halved (foot end dynamic gradient) Wnt helps maintains the gradient

Question 27

What features of planarians are important?

Answer 27

Uses the same gradient as the Hydra. If cut into peices still has ante-posterior polarity and forms a head/tail. Multipotent stem cells drive regeneration

Question 28

How does the axolotl regenerate?

Answer 28

Each cell type in the blastema de differentiates, proliferates, and then redifferentiates. No multipotent cells involved

Question 29

Whats the difference in cell differentiation between regeneration and embryo development

Answer 29

Eg. Limb: doesnt use the same genes in embryonic and regeneration (SHH and FGF are conserved)
Eg. Gut: Paneth cells are not confined to the crypt during development like they are during regeneration. Paneth cells form after CBC cells during development, but CBC needs need paneth cells to survive in regeneration

Question 30

At what stage in development are plurpotent stem cells found?

Answer 30

In the very early embryo before implantation

Question 31

stem cells n that

What cells are found in the fetus?

Answer 31

Partially specialized tissue, multipotent cells, and oligopotent cells

Question 32

What does Nanog do?

Answer 32

During compaction, the ICM is created, which transiently expresses Nanog (until implantation). ES cells comprise the ICM, and Nanog makes them pluripotent

Question 33

What is the function of LIF?

Answer 33

Maintain ES cells. ES cells can be maintained in culture (basically pausing development) by feeding them LIF. In the embryo, surrounding trophoblasts secrete LIF. Nanog pos cells are maintained during diapause due to LIF secreted.

Question 34

What are neural stem cells precursors and daughter cells?

Answer 34

Precursors: ES cells
Daughter: glilal cells and neurons