Cell determination and cell sequence Flashcards
What happens once a cell differentiates regarding mechanism for memory?
Once a cell differentiates it remembers this state even without any external inducing signal
What are the two ways for the mechanism for memory?
Chromatin remodelling and positive feedback
How does positive feedback work in terms of A and B?
Signal only affects A and is only required to start cycle between A and B
A and B can resume the cycle without signal
What is the master gene regulator for melanocytes?
MITF is the master gene regulator for melanocytes
What happens when MITF gene is homozygous?
When homozygous, the MITF gene causes loss of all melanocytes
What happens to the eyes in the loss if melanocytes?
Eyes become small due to loss of pigmented retina
What does + mean in genetics?
Means a normal gene
What does - mean in genetics?
Means a mutant gene
What does -/- mean in genetics?
Means both copies mutant
What does waadenburg syndrome 2 cause?
Deafness due to loss of pigments in ear
Congenital patchy loss of pigment in skin
Process of MC1R-cAMP signalling in melanocytes?
- MSH binds to MC1R on the membrane
- This activates Ad cyclase enzyme that form PKA which are cAMP-dependent
- CREB proteins are phosphorylated and activated by PKA
- These PCREB enter the nucleus and bind to CRE in gene promoter
This increases MITF in melanocytes via transcription
How are melanocyte-specific genes activated?
- MITF is transcribed and translated
- Produces a MITF protein
- MITF acts as a transcription factor for transcription of MC1R
Specialised proteins are made
How can melanocyte differentiation be turned on?
Melanocyte differentiation can be switched on by MSH and stabilised even without
What are myogenic factors?
master gene regulators in skeletal muscle differentiation. Can bind to DNA and E proteins
What are E proteins?
Widely expressed transcription factors
What is ID1?
A protein in myoblasts. Strongly bind to E proteins but not DNA
What is cell senescene?
Permanent cell growth arrest after extended cell proliferation
What is cell senescene strongly implicated in?
Strongly implicated in symptoms of ageing
What is cell senescene a defence against?
A major defence against cancer
What is cell lifespan?
The total number of cell doublings a cell goes thorough before senescene
What do cells sometimes have when they go into senescene?
Sometimes they’ve biological markers
What are the biological markers which are present when the cell goes into senescene?
○ Many more lysosomes in comparison to normal cells
○ Protein p16 a cell cycle inhibitor
What is a telomere
A hexamer sequence TTAGGG repeated 1000s of times at the end of the chromosome
What part of DNA not replicated normally and why?
3’ ends of DNA not replicated normally because RNA primer has to bind beyond the part to be replicated
What is required to maintain the length of the telomere?
Enzyme telomerase is needed to maintain the length of telomere
What is telomerase?
A protein-RNA complex
What does telomerase do?
Replicates telomeric DNA by reverse transcribing DNA from its own RNA
What happens to telomeres as cells divide and why?
Telomeres shorten as cell divide because normal somatic cells don’t contain TERT
How is replicative senescene triggered?
Triggered by telomeres getting to a particular short length
Why are germ line cells immortal?
Germline cells are immortal as they have TERT so telomeres remain long and cells can divide forever
What percentage of cancer cells have TERT and what does this result in ?
Approx 90% of cancer cells have TERT so divide uncontrollably
What does telomere shortening switch on?
Switches on DNA damaging signalling
This turns on p53 and then
p21
This inhibits CDK1/2 resulting in an arrest in cell divison
What does radiation, oxidative stress and DNA damage do?
○ P16 switched on which inhibits CDK4/6
RB is activated which inhibits E2F resulting in an arrest in cell division.
What are the effects on ageing?
○ Telomere length (measured in blood cells), variable, but on average falls with age. 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.
What do embryonic stem cells express?
Express TERT
What are embryonic stem cells naturally?
Naturally immortal
What type of cells are embryonic stem cells?
Totipotent though sometimes called pluripotent
Do somatic stem cells have telomerase?
Have some, but not enough to make the cell immortal
Shortening of telomeres in somatic stem cells compared to any other cell
Telomeres shorten less in somatic stem cells than any other cell however do shorten so most somatic stem cells do senesce gradually.
