Cell Differentiation, Cell Death and Stem Cells

Question 1

what does it mean if a cell is:
a) totipotent b) pleuripotent c) unipotent?

at which stage do we find these?

Answer 1

totipotent: zygote (fert. egg) - has the pontential to become any other cell in body

after gastrulation: pluripotent: cells can generate a wide variety of cells types but not all. cells are tissue type of : ectoderm, endoderm or mesoderm

(after more development) unipotent: a reserve populaation that can be used to regeneration news of one lineage

Question 3

1. what are the 3 basic categories of cells found in the body?
2. which cells don’t have genome?

Answer 3

1:

• germ cells (become sperm / ovum)
• somatic cells
• stem cells

2:

rbc and platelets

Question 4

what do transcription factors do?

how can transcription factors change cells?

Answer 4

- proteins that attach to promoter regions of gene and allow the gene to be transcribed. (if the DNA in promoter region is methylated, the transcription factor cant transcribe to the gene)

• transcription factors can turn on at different times during cell differentation
• as cells mature, different transcription factors can act on gene expression and change cells specification

-

Question 5

what can influence cell fate?

Answer 5

external signals

(e.g. can make a fat cell: pluriopotent cell & culture medium of dexamethazone and insulin = adipose cell.

(need to know these? two other examples on slide))

Question 6

what are the different commitment stages of cell differentiation?

Answer 6

1. specification: capable of differentiating autonomously wihen placed in a neutral environment, not when placed in non-neutral env. reversible. (e.g. might be liver cell but dont know yet which cell)

2. determination: capable of differentiating autonomously even when placed into another embryonic region. irreversible (committed to cell lineage bc have turned on more transcription factors).

Question 7

what can influence flexibility of cell differentiation?

Answer 7

epigenetic landscape

(process of cell fate decisions)

top of mountain: totipotent cell

bottom of mountain: differentiated cells

(need to know the different letters on

Question 9

what are progenitor cells?

Answer 9

Progenitors are typically the descendants of stem cells, only they are more constrained in their differentiation potential or capacity for self-renewal, and are often more limited in both senses.

The most important difference between stem cells and progenitor cells is that stem cells can replicate indefinitely, whereas progenitor cells can divide only a limited number of times

Question 10

what is apoptosis? why does apoptosis occur?

Answer 10

= Programmed cell death

Beneficial: removes old / damaged cell. Prevents tumour formation or cause other damage.

Process: Membrane blebbing, shrinkage of cells, nuclear collpsae, apopotic body formation, engulfed by wbc

Question 11

what is necrosis? why does necrosis occur? how does it occur?

Answer 11

Definition: Premature death of cell due to external factors

Results in inflammation.

Process: Membrane disruption, respiratory poisons and hypoxia cause ATP depletion, metabolic collapse, cell swelling and rupture.

Question 12

describe basic differences between apoptosis and necrosis mechanisms

Answer 12

necrosis:. recovery possible. occurs by: swelling of ER and mitochondria, membrane blebs, plasma membrane breaks bc can’t hold fluid inside. cells organelles released. inflammatory process undergone

(cells burst)

apoptosis: irreverisble. cells shrink and condense (including chromatin). cell fragments into apoptotic bodies. phagocytosis of apoptotic cells and fragments. avoids release of cell contents

Question 13

what can cause necrosis?

Answer 13

External factors:

• high or low temperatures
• trauma
• snake / spider bites

Internal factors:

• Immune system
• Oxidative stress

Question 14

How can you treat necrosis?

Answer 14

• Antioxidants (reverses oxidative stress). e.g. Vitamin C / E

- Surgical removal of necrotic tissue

• Maggot debridement therapy (remove necrotic tissue and suppress infection)

Question 15

where does apoptosis occur during development and in adult life?

Answer 15

Development:

• Nervous system
• Fingers and toes
• Approx. 50% more cells produced than needed

Adult:

• Between 50 & 70 b cells die each day

Question 16

why is apoptosis highly regulated?

what are two apoptopic pathways?

Answer 16

• apoptosis cannot be stopped once is has started: regulation

2 pathways:

extrinsic apoptopic pathway

• enviroment around the cell could cause cell death.
• tumour necrosis factor (TNF) binds to death receptor. activates caspases

intrinsic apoptopic pathway:

• targets the cell’s mitochondria -> activates caspases

Question 17

what are caspases? what are the two different types

Answer 17

(enzymes essential in the process of apoptosis)

all cells have caspases. want them switched off / inactive (in pro-form). only activated when intrinsic or extrinsic pathway is initiated.

Initiator caspases

• pro-caspases get activated to active caspases (Caspase 2, 8 and 9)
• intiator caspases activate the executioner caspases

Executioner caspases

• again, activated from pro-caspase to activate caspase (Caspase 3, 6 and 9 -> effector caspases)

Cause:

nuclear fragmentation, cytoskeleton disruption, membrane alterations, organelle reduction

Question 18

why are stem cells different to other cells?

what controls their activation?

Answer 18

• can divide to renew themselves indefinitedly. self renew
• can generate specialised (differentiated cell types). can be multipotent or unipotent
• environment (niche) controls their activation. (find out more?)

Question 19

explain how stem cell division occurs

Answer 19

• stem cell division: asymmetrical or symmetrical

- asymmetrical: one daughter cell becomes new stem cell, other daughter cell becomes differentiated

- symmetrical: one stem cell divides into two stem cells OR stem cell will commit two daughter cells to differential lineages. both daughter cells have same fate

• creates a constant pool or stem cells

Question 20

where do you find stem cells? classic stem cell e.g.?

Answer 20

hematopoietic stem cells: differentiate into different blood cells

loads of different cell types like:

skin, hair, gut, bone, muscle, neuronal stem cells

Question 21

how can we use stem cell in medicine?

Answer 21

regeneration of tissues that are under constant stress or damaged by trauma (e.g. hair transplant)

Question 22

what can you do with induced stem cells?

Answer 22

• patients somatic cells can be induced to be pluripotent to produce patient specific induced pluripotent stem cells (iPS)
• iPS can be induced to form ectodermal epithelial cells and neurcal crest in vitro = combine to make a tooth.

Question 24

what is sensecence?

what is it caused by?

function?

Answer 24

= irreversible proliferative arrest. if a cell is important structurally will keep it (instead of apoptosising it).

• caused by same factors that cause apoptosis (dont understand why undergo)

Question 25

describe difference between cells in newborns and old people with regards to ageing cells?

Answer 25

Newborns: large stem cell pool. tissue regeneration easy. long telomeres. no senescence

Elderly: small stem cell pool. tissue regeneration slow / reduced. short telomeres - undergo apoptosis or senescence. high senescence. few may escape senesence -> contributes to carnioma developement.

Question 26

what can happen to cells that escape cell apoptosis or senescence?

Answer 26

escaped cells may:

• up regulate telomerase (goes back to younger phenotype)
• INK4A is a tumour suppressor can be lost -> increaes likelihood of cancer

Question 27

why might cancer stem cells appear?

Answer 27

• cancer stem cells might appear after mutations in specific stem cells, stem cell progenitors or from differentiated cells.
• niche changes and lead to tumours

Question 28

what happens to apoptosis and senescence regarding cancer?

Answer 28

cancer causes a loss of apoptosis and senescence:

pre-malignant tumour: mixed population of cell ages and types

malignant tumour: favour of proliferation