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Cell Differentiation, Determination & Senescence Flashcards

1
Q

What is cell differentiation?

A

Production of different cell types within an organism

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2
Q

What is another name for a new expression pattern?

A

Program differentiation

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3
Q

Give an example of when modulation occurs?

A

The up regulation of alcohol dehydrogenase in hepatocytes

- when blood alcohol levels increase

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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

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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

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6
Q

What is De Novo methylation?

A

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

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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

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8
Q

What is a cell lineage?

A

The developmental history of a differentiated cell from the zygote

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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)
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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!!!

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11
Q

What are Household genes?

A

Genes that are transcribed in (nearly) all cell types

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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

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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

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14
Q

What is the role of Master gene regulators?

A

Regulate transcription of a program for a given cell type

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15
Q

What can cause a change in gene expression?

A
  • Mutations
  • Differentiation
  • Modulation
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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
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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

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18
Q

Why do some cell lineages branch into different cell types?

A

When the precursors are pluripotent they differentiate into various cell types

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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

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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

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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

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22
Q

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

A
  • MITF in melanocytes

- MYOD1 in skeletal muscles

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23
Q

How does differentiation and modulation differ?

A

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

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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
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25
What is the consequence of methylation?
Methylation of a gene , especially on a promoter, silences the gene
26
What is modulation?
A simple reversible change in gene expression dependent on a continuous external stimulus no change to the cell type
27
What is MTIF?
Master regulator gene that forms a master regulator protein called MTIF protein
28
How is heterochromatin structured?
Not in use during transcription so tightly coiled and folded so transcription enzymes can't access it
29
What are Master Gene Regulators?
Type of Transcription Factors
30
Give an example of household genes
Metabolic enzymes
31
How do the genes expressed differ within an organism?
Different cell type within the same organsims have the same genes
32
Describe the structure of euchromatin when in use
Mainly active and in use so is in an unfolded, open conformation
33
Why is methylation of globin genes developmentally regulated?
Globin genes are expressed in the RBC lineage only | their promoters are therefore methylated in other cell types
34
What is gene expression?
The process leading to synthesis of a final gene product (protein, functional gene etc.)
35
What are luxury genes?
Specialised genes present in only certain cell types
36
Name the Myogenic regulatory factors in skeletal muscle
MyoD, Myf5, MyoG, MRF4
37
What occurs at each stage of differentiation?
At each step, an immature cell type (precursor) changes into a more mature cell type, which may still be a precursor
38
What is cell senescence?
The permanent cell growth arrest after extended cell proliferation
39
How are some terminally differentiated cells replaced?
Some are constantly replaced by the division of precursor cells (somatic stem cells)
40
Why is comparing mRNA a good way of detecting differentiation?
Certain proteins are only seen in specific cells alone
41
What is cell determination?
Memory of cell differentiation and mechanisms in cell types
42
Give an example of master gene regulators
MYOD (myogenic differentiation) in skeletal muscle | - activate a program of muscle specific genes
43
Give examples of cells that can't divide
Neurons or Lens | Can't divide so aren't replaced when lost
44
How can we view specific proteins within a cell type?
Using immunostain we can use specific anitbodies to stain proteins
45
List ways transcription is controlled in the body?
1. Chromatin remodelling/folding - DNA methylation - De novo methylation 2. Specific transcriptional regulation of individual genes - TF
46
What is the significance of differentiation in cancer?
Differentiation is often deficient in cancers | Tumour cells resemble blast cell/stem cells e.g. neuroblasts
47
How many chromosomes are there in a body cell?
A human somatic cell contains 46 chromosomes
48
What is the consequence of birth differentiation defects?
Differentiation defects at birth are often lethal but there are some uncommon non lethal defects
49
Why does positive feedback result in transcription without a signal?
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
Name some somatic stem cells
Bone marrow cells Gut epithelium Epidermis
51
Using the example of Dolly the Sheep, how do we know that differentiated cells have a complete genome?
- 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
What is the cell lineage of skeletal muscle cells?
somite cell -> myotome cell -> migrating myoblasts -> skeletal muscle
53
Explain what is meant by a program?
A whole set of lineage specific genes
54
How does differential gene expression occur?
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
How is specific transcriptional regulation of individual genes carried out?
By transcription factors that fit specifically onto specific DNA sequences of genes either increasing or reducing transcription
56
What are E proteins?
Enhancer proteins that are widely expressed Transcription factors
57
Explain how MITF genes in melanocytes are transcribed using positive feedback
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
How is chromatin remodelled to regulate transcription?
States of DNA methylation and histone modification occur which are copied to daughter cells
59
What is the consequence of a mutation in human melanocytes?
In humans, Heterozygous MITF mutation causes Waardenburg syndrome causes deafness and congenital patchy pigment loss
60
What are the 2 major ways transcription of genes is controlled in cells?
1. Chromatin remodelling | 2. Positive feedback / Specific regulation
61
What is a cell's lifespan?
The total no. of cell divisions a cell undergoes before senescence
62
What is ID1?
Protein coding genes present in myoblasts
63
How can the differentiation of melanocytes cause disease in mice?
Homozygous MITF mutation causes pigment loss in their retinas
64
How do master gene regulators lead to the development of a specific tissue?
Master gene regulators specifically regulate the transcription of certain genes in cells which once differentiated remember without any external inducing signal
65
Under normal conditions, how do the MYOD1 family activate promoters in skeletal muscle?
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
Describe the structure of myogenic regulatory factors in skeletal muscle
Basic helix loop helix transcription factors regulating myogenesis - 4 interacting master gene regulators
67
Why can melanocyte differentiation occur even without the presence of MSH?
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
List some of the muscle genes activated by the MYOD1 family
- Actin - Myosin - Muscle Creatine Kinase - Desmin - AchR
69
How does the presence of ID1 inhibit differentiation?
ID1 binds strongly to E proteins - MYOD1 can't bind anymore Prevents activation of muscle gene promoters ID1 inhibits differentiation
70
What is the role of Telomerase Reverse transcriptase (TERT)?
Reverse transcribes DNA from its own telomeric RNA
71
How do cells undergo senescence?
Somatic cells senescence gradually as they don't contain telomerase reverse transcriptase so the telomeres shorten as the cell divides
72
What is replicative senescence?
A limitation in the number of times a cell can divide triggered by telomeres at a particular length
73
What is P16?
A tumour supressor gene, in humans encoded by CDKN2A gene
74
How is senescence thought to cause ageing?
On average telomere length decreases with age Ageing tissues express more P16 proteins - cause defective telomerase gene subunits => premature ageing and early death
75
How are germline cells immortal?
They contain TERT so their telomeres remain long | - these cells can divide infinitely
76
What is the role of P16 in cell senescence?
Plays important role in cell cycle regulation by decelerating the cell's progression from the G1 to S phase
77
What can a deficiency in P16 result in?
P16 lows associated with human senile defects e.g. - Cardiovascular - Fratility - Diabetes - Cancer - Neurodegeneration
78
How is TERT associated with cancer?
90% of cancer and tumour cells contain TERT - resulting in uncontrollable cell division
79
What abnormalities are present in cancer cells?
- TERT expression - P53 defects - P16 defects
80
What is telomerase?
aka Terminal transferase enzyme | Protein RNA complex that replicates telomeric DNA
81
How is telomere length maintained?
Via telomerase enzyme continuously adding species-dependent telomere repeat sequence to the 3' end of telomeres
82
How does cell senescence occur?
Occurs in telomeres when the sequence TTAGGG is repeated 1000's of times - the 3' end of DNA is therefore not replicated normally
83
What common biological markers are present in cells ready for senescence?
- Excess lysosome number compared to normal | - P16 presence (cell cycle inhibitor)

FLC (34 decks)

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