Cell differentiation and scenescence

Question 1

What is cell determination?

Answer 1

• Cell determination process whereby cell fate becomes stable. It is followed by cell differentiation. When a cell chooses a particular “fate”, it is said to be determined. Implies a stable change.

Question 2

Compare and contrast cell differentiation and cell determination

Answer 2

On slide images

Question 3

Describe asymmetrical cell division

Answer 3

Asymmetrical cell division due to differential distribution of cytoplasmic molecules (proteins or mRNAs) within a cell before it divides

The two daughter cells = different fates= different gene expression profile.

Question 4

What is the most common cause of cell determination

Answer 4

Inductive signals from neighbouring cells is the most common cause.

One group of cells influences the development of another group of cells.

Question 5

What are pioneer factors?

Answer 5

Pioneer factors/master regulators together with co-factors are key in cell-fate decision making.

that access silent chromatin, remodel it and initiate cell-fate.

Highly expressed in embryonic stem cells and needed to maintain their pluripotency.

Can activate or inhibit gene expression:

Histone modification
DNA methylation blockage

Question 6

What is cellular senescence and what causes it?

Answer 6

• Cell senescence: irreversible cell-cycle arrest mechanism in which cells cease to divide.

Occurs as response to excessive extracellular or intracellular stress.

Question 7

What is the purpose of cellular senescence?

Answer 7

It is major defence against cancer.

Strongly implicated in symptoms of ageing.

Question 8

What is the hayflick limit?

Answer 8

The number of times that a normal human cell population will divide before cell division stops.

Question 9

What is cell lifespan?

Answer 9

Cell lifespan is the total number of doublings that a cell population goes through before senescence.

Question 10

What are the 5 morphological changes as a result of cell senescence?

Answer 10

Larger and flat cells

- Prominent nucleoli
- Nuclear lamina degradation
- Vacuolised
- Chromatin reorganisation

Question 11

What are the biochemical and molecular changes

Answer 11

Go over

Question 12

What are the telomeres?

Answer 12

Easy recall question

Question 13

What happens when the telomeres are broken?

Answer 13

Unstable and join with other chromosomes and undergo recombination
degraded
damage of telomere flanking genes

Question 14

What is the shelterin protein?

Answer 14

Folding of telomeric DNA facilities folding which shields the chromosome

Question 15

Why do telomeres progressively get shorter?

Answer 15

Progressive telomere shortening occurs in all dividing normal cells mainly due to incomplete lagging-strand DNA synthesis/replication of that area.

Question 16

What is telomerase?

Answer 16

Ribonucleoprotein enzyme which replicates telomeric DNA by reverse transcribing DNA hexamers (TTAGGG) from RNA using its RNA subunit (TERC- telomerase RNA component) and its protein component (TERT- telomerase reverse transcriptase).

Question 17

Is telomerase present in adult somatic cells?

Answer 17

Mainly absent from adult cells, only present in highly-proliferative such as blood, skin and intestine.

Question 18

What process prevents telomeres from getting too short?

Answer 18

Replicative senescence is triggered in normal cells when telomere(s) get quite short. (About 1-5 short telomeres sufficient).

Question 19

Why are germline cells immortal and can divide forever?

Answer 19

Germline cells (oocytes, sperm and their diploid progenitors) do express TERT so they maintain full-length telomeres. Hence germline is immortal-cells can divide forever.

Question 20

Describe telomeres and cancer

Answer 20

Nearly all cancer cell lines in culture (~90%) express TERT, so they are immortal.

Telomere shortening represents a major barrier to tumorigenesis, operating as a tumour suppressor pathway; however activation of telomerase provides an escape from crisis and allows outgrowth of cells with a rearranged genome.

Question 21

Some of the commonest abnormalities found in cancer cells are those leading to defective senescence & immortality:

Answer 21

Expression of TERT
p53 defects
p16 defects.

Question 22

What is the evidence for telomeres getting shorter as people age, and how healthy you are?

Answer 22

Telomere length typically very short in people aged >100.

• p16 and other senescence-associated proteins are expressed increasingly in ageing tissues.
• Telomere length at birth varies between people: genetically linked to age at death.
• Defective genes for telomerase subunits give syndromes with premature ageing and early death.
• p16 (CDKN2A) locus also genetically associated with human senile defects – cardiovascular disease, frailty, type II diabetes, neurodegeneration, cancer.