Cell Determination + Cell Senescence

Question 1

What is mechanism for memory in cell differentiation?

Answer 1

Chromatin remodelling 
Positive feedback (feed forward)

Question 2

Positive feedback is illustrated by 2 specific examples of master gene regulators in differentiation

Answer 2

Melanocytes

e.g. skeletal muscle, MYOD1 family + MITF

Question 3

Mutations of 1 copy of MITF gene in humans causes …..

Answer 3

Waardenburg syndrome 2

Deafness + congenital patchy loss of pigment=> in skin + can include irises

Question 4

What are 4 interacting master gene regulators in skeletal muscle differentiation?

Answer 4

MYOD1, MYF5, MYOG + MRF4

Question 5

What is ID1 (inhibitor of differentiation 1)?

Answer 5

Protein in myoblasts (muscle precursor cells) which can strongly bind E proteins but not DNA

Question 6

What is cell senescence?

Answer 6

Major defence against cancer

Strongly implicated in symptoms of ageing

Question 7

What does growth arrest mean?

Answer 7

Finite lifespan + is measured in population doublings

Question 8

What does cell lifespan mean?

Answer 8

Total doubling that cell population goes through before senescence

Question 9

What are telomeres?

Answer 9

1000s of repeats of hexamer sequence at chromosome ends

Question 10

What is telomerase enzyme?

Answer 10

Is protein-RNA complex that can replicate telomeric DNA hexamers from its own RNA sequence +joining them to chromosome ends

Question 11

What is function of telomerase enzymes?

Answer 11

Is needed to maintain telomere length

Question 12

What is TERT?
In what cells,are they expressed?
In what cells, are they not expressed?

Answer 12

Telomerase reverse transcriptase
Normal germ line do express TERT so they maintain full-length telomeres
Cancer cells in culture nearly all express TERT
In humans, most somatic cell express no TERT so no telomerase activity therefore telomeres shorter as cells divide

Question 13

Give examples of germ line

Answer 13

Oocytes + sperm and their diploid progenitors

Question 14

What are Some of commonest abnormalities found in cancer cells are those leading to defective senescence + immortality

Answer 14

Expression of TERT
p53 defects
p16 defects

Question 15

Cell senescence + ageing

Answer 15

Telomere length is variable but on average falls with age
p16 + other senescence associated proteins are expressed increasingly in ageing tissues
Telomere length at birth varies between people genetically to age at death
Defective gene for telomerase subunits give syndromes with premature ageing + early death
P16 locus generically associated with human senile defects=> cardiovascular disease, frailty, type II diabetes, neurodegeneration, cancer

Question 16

What is stem cells?

Answer 16

A cell that is capable of both self-replication + differentiation into one or more kinds of specialised, functional cells

Question 17

What is unipotent stem cells?

Answer 17

Can form only one functional cell type

Question 18

What is pluripotent stem cell?

Answer 18

Can form several functional cell types

Question 19

What is totipotent stem cell?

Answer 19

Can form all functional cell types including placenta

Question 20

What are embryonic stem cells?

Answer 20

Cells of inner cell mass of early mammalian embryo can act as totipotent stem cells called embryonic stem cells

Question 21

Give examples of connection between cell senescence + ageing symptoms

Answer 21

Bone marrow: older people show decreased immunity, increased bone failure, reduced proliferative ability of marrow stem cells
Hair greying: linked to decreased melanocytes stem cell maintenance in hair follicles
Reduced healing ability of skin with age, increased risk of skin ulcers