Cell Differentiation, Determination & Senescence Flashcards Preview

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Flashcards in Cell Differentiation, Determination & Senescence Deck (83)
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1
Q

What is cell differentiation?

A

Production of different cell types within an organism

2
Q

What is another name for a new expression pattern?

A

Program differentiation

3
Q

Give an example of when modulation occurs?

A

The up regulation of alcohol dehydrogenase in hepatocytes

- when blood alcohol levels increase

4
Q

Experimentally how is differential transcription detected?

A

Using individual probes or microarrays we can test 1000’s of unknown RNAs
- reveals any mRNA differences between 2 cell types

5
Q

What is cell determination?

A

The stability of cell differentiation even after any inducing signal has been transmitted to daughter cells after division

6
Q

What is De Novo methylation?

A

Unmethylated CpG pairs get methylated during differentiation and gamete formation by de Novo
methyltransferase enzyme

7
Q

How does MTIF protein regulate transcription of genes?

A

MTIF gene undergoes transcription & translation -> MTIF protein
MTIF protein binds to program promoters activating them
Program genes are translated into specialised proteins

8
Q

What is a cell lineage?

A

The developmental history of a differentiated cell from the zygote

9
Q

Which sites on a gene can Transcription factors bind to in order to alter transcription
of that gene?

A
  1. Transcriptional Start site (TATA box - basal promoter)
  2. Promoter Region (motifs and sequences complementary to TF)
  3. Enhancers (3’ of gene or in introns)
10
Q

What do the branches on cell lineage diagrams represent?

A

Branches represent the different cell types each precursor can differentiate into
Does not represent cell division!!!

11
Q

What are Household genes?

A

Genes that are transcribed in (nearly) all cell types

12
Q

Give an example of cell determination

A

Different types of Blood cells

- they’re all in the same environment but remember what cell type they all are

13
Q

How do different TFs activate different genes?

A

Via the specific binding elements in their promoters and enhancers
Different cell types express different TFs, transcribing different sets of genes

14
Q

What is the role of Master gene regulators?

A

Regulate transcription of a program for a given cell type

15
Q

What can cause a change in gene expression?

A
  • Mutations
  • Differentiation
  • Modulation
16
Q

Compare the mRNA differences between skeletal muscle and melanocytes

A

Skeletal Muscle Protein mRNA

  • muscle actin
  • muscle creatine kinase
  • myoglobin

Melanocytes Protein mRNAs

  • Tyrosinase
  • sopachrome
  • tautomerase
  • myosin 5a
17
Q

What type of division pattern do Liver endothelium cells follow?

A

Liver endothelial cells divide very little but divide to repair any cell damage

18
Q

Why do some cell lineages branch into different cell types?

A

When the precursors are pluripotent they differentiate into various cell types

19
Q

How does methylation cause heterochromatin formation?

A

DNA methylation tends to occur in whole stretches of DNA rich in CpG pairs
methylated DNA becomes highly folded -> heterochromatin

20
Q

Give examples of non lethal differentiation birth defects?

A

Aniridia
- lack of eye iris due to PAX6 mutation

Congenital Anaemia & thrombocytopenia
- Mutation of GATA1 TF responsible for erythrocyte and platelet differentiation

21
Q

How does DNA Methylation occur?

A

Cytosine in a CpG pair is methylated
Methylation is copied to daughter strands (as copied to opposite strand)
methylation pattern is remembered in daughter cells

22
Q

Name the 2 common examples of master gene regulators illustrating the positive feedback mechanism

A
  • MITF in melanocytes

- MYOD1 in skeletal muscles

23
Q

How does differentiation and modulation differ?

A

Differentiation: Stable, complex change
Modulation: Temporary, simple change

24
Q

What are the 3 main division patterns of mature differentiated cells?

A
  • Very little division but for repair damage
  • Terminal differentiation - cells don’t divide
  • Precursor division
25
Q

What is the consequence of methylation?

A

Methylation of a gene , especially on a promoter, silences the gene

26
Q

What is modulation?

A

A simple reversible change in gene expression dependent on a continuous external stimulus no
change to the cell type

27
Q

What is MTIF?

A

Master regulator gene that forms a master regulator protein called MTIF protein

28
Q

How is heterochromatin structured?

A

Not in use during transcription so tightly coiled and folded so transcription enzymes can’t access it

29
Q

What are Master Gene Regulators?

A

Type of Transcription Factors

30
Q

Give an example of household genes

A

Metabolic enzymes

31
Q

How do the genes expressed differ within an organism?

A

Different cell type within the same organsims have the same genes

32
Q

Describe the structure of euchromatin when in use

A

Mainly active and in use so is in an unfolded, open conformation

33
Q

Why is methylation of globin genes developmentally regulated?

A

Globin genes are expressed in the RBC lineage only

their promoters are therefore methylated in other cell types

34
Q

What is gene expression?

A

The process leading to synthesis of a final gene product (protein, functional gene etc.)

35
Q

What are luxury genes?

A

Specialised genes present in only certain cell types

36
Q

Name the Myogenic regulatory factors in skeletal muscle

A

MyoD, Myf5, MyoG, MRF4

37
Q

What occurs at each stage of differentiation?

A

At each step, an immature cell type (precursor) changes into a more mature cell type, which may still be a precursor

38
Q

What is cell senescence?

A

The permanent cell growth arrest after extended cell proliferation

39
Q

How are some terminally differentiated cells replaced?

A

Some are constantly replaced by the division of precursor cells (somatic stem cells)

40
Q

Why is comparing mRNA a good way of detecting differentiation?

A

Certain proteins are only seen in specific cells alone

41
Q

What is cell determination?

A

Memory of cell differentiation and mechanisms in cell types

42
Q

Give an example of master gene regulators

A

MYOD (myogenic differentiation) in skeletal muscle

- activate a program of muscle specific genes

43
Q

Give examples of cells that can’t divide

A

Neurons or Lens

Can’t divide so aren’t replaced when lost

44
Q

How can we view specific proteins within a cell type?

A

Using immunostain we can use specific anitbodies to stain proteins

45
Q

List ways transcription is controlled in the body?

A
  1. Chromatin remodelling/folding
    • DNA methylation
    • De novo methylation
  2. Specific transcriptional regulation of individual genes
    • TF
46
Q

What is the significance of differentiation in cancer?

A

Differentiation is often deficient in cancers

Tumour cells resemble blast cell/stem cells e.g. neuroblasts

47
Q

How many chromosomes are there in a body cell?

A

A human somatic cell contains 46 chromosomes

48
Q

What is the consequence of birth differentiation defects?

A

Differentiation defects at birth are often lethal but there are some uncommon non lethal defects

49
Q

Why does positive feedback result in transcription without a signal?

A
  1. A signal causes a component (A) to be activated/made
  2. Once (A) activated causes (B) to also be activated
  3. (B) activated, causes more (A) to be activated - creates a cycle
  4. => positive feedback - signal no longer required
50
Q

Name some somatic stem cells

A

Bone marrow cells
Gut epithelium
Epidermis

51
Q

Using the example of Dolly the Sheep, how do we know that differentiated cells have a complete genome?

A
  • A whole differentiated sheep cell was fused to
    cytoplasm of a sheep oocyte
  • resulting cell proliferated into a whole early embryo
    (dolly the sheep)
  • Differentiated cells had all the genes required to
    produce a whole organism
52
Q

What is the cell lineage of skeletal muscle cells?

A

somite cell -> myotome cell -> migrating myoblasts -> skeletal muscle

53
Q

Explain what is meant by a program?

A

A whole set of lineage specific genes

54
Q

How does differential gene expression occur?

A

During mRNA transcription, in each cell lineage step

  1. Diverse cell type specific genes are activated in expression
  2. Others are repressed
  3. New expression pattern is formed
55
Q

How is specific transcriptional regulation of individual genes carried out?

A

By transcription factors that fit specifically onto specific DNA sequences of genes either increasing
or reducing transcription

56
Q

What are E proteins?

A

Enhancer proteins that are widely expressed Transcription factors

57
Q

Explain how MITF genes in melanocytes are transcribed using positive feedback

A
  1. MSH-MC1R complex signalling switches on cAMP
  2. cAMP activates CREB cycle
  3. CREB cycle enables MC1R transcription switching on
    MITF
  4. Cycle continues transcribing more MC1R and MITF
58
Q

How is chromatin remodelled to regulate transcription?

A

States of DNA methylation and histone modification occur which are copied to daughter cells

59
Q

What is the consequence of a mutation in human melanocytes?

A

In humans, Heterozygous MITF mutation causes Waardenburg syndrome causes deafness and congenital patchy pigment loss

60
Q

What are the 2 major ways transcription of genes is controlled in cells?

A
  1. Chromatin remodelling

2. Positive feedback / Specific regulation

61
Q

What is a cell’s lifespan?

A

The total no. of cell divisions a cell undergoes before senescence

62
Q

What is ID1?

A

Protein coding genes present in myoblasts

63
Q

How can the differentiation of melanocytes cause disease in mice?

A

Homozygous MITF mutation causes pigment loss in their retinas

64
Q

How do master gene regulators lead to the development of a specific tissue?

A

Master gene regulators specifically regulate the transcription of certain genes in cells which
once differentiated remember without any external inducing signal

65
Q

Under normal conditions, how do the MYOD1 family activate promoters in skeletal muscle?

A

Myogenic factors work as dimers with E proteins

  1. MYOD1 and E proteins bind to DNA promoter site
  2. MYOD1 and Myf5 bind to activate gene muscle
    promoters
66
Q

Describe the structure of myogenic regulatory factors in skeletal muscle

A

Basic helix loop helix transcription factors regulating myogenesis
- 4 interacting master gene regulators

67
Q

Why can melanocyte differentiation occur even without the presence of MSH?

A

MC1R has some basal activity without MSH ligand
- once MC1R is present some cAMP and MITF continue to
be made even if MSH isn’t present
- melanocyte differentiation can occur with and without
MSH

68
Q

List some of the muscle genes activated by the MYOD1 family

A
  • Actin
  • Myosin
  • Muscle Creatine Kinase
  • Desmin
  • AchR
69
Q

How does the presence of ID1 inhibit differentiation?

A

ID1 binds strongly to E proteins - MYOD1 can’t bind anymore
Prevents activation of muscle gene promoters
ID1 inhibits differentiation

70
Q

What is the role of Telomerase Reverse transcriptase (TERT)?

A

Reverse transcribes DNA from its own telomeric RNA

71
Q

How do cells undergo senescence?

A

Somatic cells senescence gradually as they don’t contain telomerase reverse transcriptase so
the telomeres shorten as the cell divides

72
Q

What is replicative senescence?

A

A limitation in the number of times a cell can divide triggered by telomeres at a particular length

73
Q

What is P16?

A

A tumour supressor gene, in humans encoded by CDKN2A gene

74
Q

How is senescence thought to cause ageing?

A

On average telomere length decreases with age
Ageing tissues express more P16 proteins
- cause defective telomerase gene subunits
=> premature ageing and early death

75
Q

How are germline cells immortal?

A

They contain TERT so their telomeres remain long

- these cells can divide infinitely

76
Q

What is the role of P16 in cell senescence?

A

Plays important role in cell cycle regulation by decelerating the cell’s progression from the G1 to
S phase

77
Q

What can a deficiency in P16 result in?

A

P16 lows associated with human senile defects e.g.

  • Cardiovascular
  • Fratility
  • Diabetes
  • Cancer
  • Neurodegeneration
78
Q

How is TERT associated with cancer?

A

90% of cancer and tumour cells contain TERT - resulting in uncontrollable cell division

79
Q

What abnormalities are present in cancer cells?

A
  • TERT expression
  • P53 defects
  • P16 defects
80
Q

What is telomerase?

A

aka Terminal transferase enzyme

Protein RNA complex that replicates telomeric DNA

81
Q

How is telomere length maintained?

A

Via telomerase enzyme continuously adding species-dependent telomere repeat sequence
to the 3’ end of telomeres

82
Q

How does cell senescence occur?

A

Occurs in telomeres when the sequence TTAGGG is repeated 1000’s of times
- the 3’ end of DNA is therefore not replicated normally

83
Q

What common biological markers are present in cells ready for senescence?

A
  • Excess lysosome number compared to normal

- P16 presence (cell cycle inhibitor)