Apoptosis and quiescence lectures

Question 1

Apoptosis define

Answer 1

Eliminates cells with DNA damage that fail to be repaired at G1/S or G2/M
Crucial to cell number and morphogenesis
eg. eliminates self-lymphocytes

Question 2

What morphology of apoptosis can be observed under a microscope?

Answer 2

Cell shrinkage, nuclear condensation/fragmentation, chromosome condensation, releasing apoptotic bodies containing organelles, blebbing(bulges)

Question 3

How do macrophages recognise apoptotic cells?

Answer 3

Phoshatidylserine exposure (which is usually in cytoplasmic portion of PM)

Question 4

What did C Elegans studies reveal?

Answer 4

Pro- (BAX, BAK) and anti- (BCL2 and BCL-XL)apoptotic factors, executioner factors (proteolytic enzymes) which cause cascade of digestion destroying cellular contents

Question 5

What ultimately triggers a proteolytic cascade?

Answer 5

Mitochondria

Question 6

What is apoptosis triggered in response to?

Answer 6

DNA damage, loss of growth factor signalling, loss of contact with basement membrane, ER stress(accumulation of unfolded proteins in ER lumen)

Question 7

Draw diagram of BAX and BAK causing apoptosis

Answer 7

See notes for diagram

Question 8

What receptor family are important in triggering apoptosis?

Answer 8

Death domain

Question 9

What do death domain receptors bind?

Answer 9

TNF alpha (produced by macrophages) or FasL (on surface of cytotoxic lymphocytes produced in immune response)

Question 10

What is quiescence?

Answer 10

Cells exit cell cycle, used by memory lymphocytes to preserve pathogen memory

Question 11

In quiescence:

Answer 11

Cells lower metabolic energy, exit cell cycle, reduce ribosome biogenesis and protein production
Wait until external signal for active cycling
Minimal damage from ROS and low chance of mutation

Question 12

What is a cell niche?

Answer 12

Allows necessary cell-cell and cell-matrix interactions, could promote quiescence eg. CDK inhibitors preventing G1 entry

Question 13

Where are epidermal stem cells?

Answer 13

Deepest most basal layer of skin (hypodermis), protected by melanin

Question 14

Epidermal stem cells…

Answer 14

Regularly regenerate the entire skin, are quiescent but can be activated at any point

Question 15

What is the point of a 3’ UTR?

Answer 15

Allows low translational activity in quiescence, miRNAs bind and prevent translation of mRNA with 3’ UTR (NB mRNA is normally translated 5’ to 3’)

Question 16

Draw stem cell diagram

Answer 16

See notes for diagram

Question 17

How are quiescent cells poised to reenter the cell cycle?

Answer 17

They have loose DNA and histones allowing TF access, histones have post-translational modifications typical of active transcriptional state
RNA pol kept paused due to binding by negative regulators preventing transcription

Question 18

What happens upon cell activation?

Answer 18

RNA pol is released, there is no need to reset transcriptional programme, cell is good to go

Question 19

What is fancy name for increase in cell size?

Answer 19

Hyperplasia

Question 20

Increase in cell no=?

Answer 20

Hypertrophy

Question 21

What is the growth law in bacteria?

Answer 21

Larger cells proliferate faster and thus maintain cell size uniform under steady state

Question 22

When is uniform cell size lost in multicellular organisms?

Answer 22

In injury and cancer

Question 23

What happens to WAC

Answer 23

They expand in number in late embryonic life to a stable number, so adipose tissue grows by accumulation of lipid particles due to diet and no increase in number (hypertrophy)

Question 24

What factor regulates adipocyte development and height?

Answer 24

Insulin growth factor 1

Participates in cartilage hypertrophy during bone formation of growing limb bones in adolescents

Question 25

What does research show about amount eaten as child and liklihood of being obese?

Answer 25

The more you eat as a baby the more likely you are to be obese because no. adipose cells set v early, cells store more fat if you eat more as a child

Question 26

In pregant women beta cells…

Answer 26

Increase in size not number to meet higher blood glucose demands, to make more insulin, as increasing in size is less risky for mistake/cancer than increasing in number