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CEDB30004 Stem Cells in Development and Regeneration > MST1 L1-13 Questions > Flashcards

MST1 L1-13 Questions Flashcards

1
Q

ES cells cannot be isolated from:

a. Blastocyst
b. Neonate nerves
c. Umbilical cord blood
d. Amniotic Fluid

A

b. Neonate nerves

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2
Q

What is true about pluripotent stem cells?

a. Primordial germ cells give rise to embryonic germ cells
b. Oct4, Sox2 and Nanog are only found in ES cells
c. EGCs are haploid and come from the PGCs of the gonads
d. Embryonic germ cells can be derived from the inner cell mass

A

a. Primordial germ cells give rise to embryonic germ cells

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3
Q

What is not a feature shared by stem cells?

a. The ability to sense extrinsic signals and react intrinsically
b. Specialised cell cycles and high telomerase activity
c. Chromatin remodelling abilities
d. Susceptible to stress

A

d. Susceptible to stress

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4
Q

• Multipotency refers to a cells ability to form derivatives of all 3 germ layers.

A

F (pluri)

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5
Q

• ‘Stemness’ refers to the idea that common molecular process (e.g. RNA transcripts) underlay the properties of self-renewal and differentiation.

A

T

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6
Q

What is false about mouse pre-implantation development?

a. The early blastocyst is at the 64 cell stage on day 3.5
b. The ICM separates into the epiblast and hypoblast
c. The main components of the blastocyst are the trophoblast, inner cell mass and neural crest
d. The outer layer (zona pellucida) specifies the species of the embryo

A

c. The main components of the blastocyst are the trophoblast, inner cell mass and neural crest

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7
Q

Which is the correct match for the derivatives of the three primary germ layers?

a. Endoderm: pancreatic cell, thyroid cell, lung cell
b. Mesoderm: Skin cell, neuron, pigment cell
c. Ectoderm : Skin cell, RBC, kidney tubule cell
d. Mesoderm: pancreatic cell, neuron, pigment cell

A

a. Endoderm: pancreatic cell, thyroid cell, lung cell

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8
Q

What is true about the tests for pluripotent stem cells?

a. Teratoma formation is the most stringent test
b. In germline chimerism, the embryo is only composed of cells from the injected ES cells
c. In vitro tests are more stringent than in vivo tests but do not test the ability to promote normal development
d. Test three does not test for complete pluripotency

A

d. Test three does not test for complete pluripotency

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9
Q

What is not a feature of mouse ES stem cell colonies?

a. They express Oct4, nanog and sox2
b. They have a flat colony morphology
c. They maintain a normal karyotype
d. They express AP and SSEA-1

A

b. They have a flat colony morphology

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10
Q

A feature that differentiates human ES cells from mouse ES cells is:

a. Their dependence on LIF
b. Their rounded colony morphology
c. Their passaging as single cells
d. Their requirement for Activin and FGF in serum and feeder free culture

A

d. Their requirement for Activin and FGF in serum and feeder free culture

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11
Q

What is not a feature of Naïve and Primed mouse ES cells?

a. Both can form chimeras
b. Both express Oct4, nanog, sox2
c. Only primed (EpiSC) have differentiation factors (brachyury and FGF5)
d. LIF only causes self-renewal in naïve mouse ES cells

A

a. Both can form chimeras

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12
Q

• During fertilisation and implantation, the egg sheds excess DNA to polar bodies.

A

T

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13
Q

• The trophoblast forms the embryo and the Inner Cell Mass forms the placenta.

A

F

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14
Q

• Cells of the embryo are totipotent up until the 8 cell stage.

A

T

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15
Q

• The zona pellucida is responsible for species specificity.

A

T

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16
Q

• Mouse ES cells can be derived from the hypoblast at the late blastocyst stage.

A

F (epiblast)

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17
Q

• LIF supresses ectoderm and BMP supresses mesoderm and endoderm.

A

F

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18
Q

• Human stem cells share many characteristics with epiblast stem cells which suggests they are from a later stage of development than mouse ES cells.

A

T

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19
Q

Which does not confer pluripotency?

a. Nanog
b. Oct4
c. BMP
d. Sox2

A

c. BMP

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20
Q

Which is most likely to be repressed by a core pluripotency regulator?

a. A mesoderm inducing factor
b. Chromatin remodelling factor
c. TGFB signalling
d. Nanog

A

a. A mesoderm inducing factor

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21
Q

Which is most likely to be activated by a core pluripotency regulator?

a. A neurogenesis inducing factor
b. Euchromatin
c. Chromatin remodelling factors
d. BMP signalling

A

c. Chromatin remodelling factors

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22
Q

What is true about the bivalent chromatin state?

a. The regulatory regions in ES cells only have repressive histone modifications
b. Differentiation genes can be permanently switched off in ES cells
c. Differentiation gene repression is only permanent in EpiSC
d. Differentiation genes in ES cells are silent but poised for activation

A

d. Differentiation genes in ES cells are silent but poised for activation

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23
Q

How can inhibitors impact mouse ES cells?

a. PDO3 can inhibit FGF and prevent differentiation and increase Nanog expression
b. Blocking GSK3 signalling increases Nanog expression and reduces differentiation
c. High levels of Nanog can inhibit FGF and Mek/ERK signalling
d. CHIR can inhibit the activity of FGF and GSK3 to prevent differentiation

A

a. PDO3 can inhibit FGF and prevent differentiation and increase Nanog expression

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24
Q

What is false about 2i culture?

a. PDO3 and LIF block differentiation
b. The level of Nanog fluctuates and the cells are in a bivalent state
c. CHIR prevents the activity of GSK3 and this promotes self-renewal
d. All cells in the culture are in the ground state and express high levels of Nanog

A

b. The level of Nanog fluctuates and the cells are in a bivalent state

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25
Q

• Oct4, Sox2 and Nanog have the capacity to regulate each other and themselves (autocrine).

A

T

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26
Q

• All mouse ES cells in conventional culture express Oct4 and Nanog at stable levels.

A

F

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27
Q

• ES cells maintain pluripotency at the ground state and become primed for a specific linage when they become progenitor cells.

A

T

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28
Q

• LIF activates self-renewal and blocks differentiation.

A

T

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29
Q

What happens during late reprogramming of iPS cells?

a. Mesenchymal epithelial transition
b. Retroviral vectors are expressed
c. Somatic genes are hypermethylated
d. Chromatin remodelling complexes are recruited

A

c. Somatic genes are hypermethylated

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30
Q

What happens during infection with Yamanaka Factors?

a. During the random phase, endogenous Sox2 regulates the expression of Oct4
b. The ordered phase precedes the random phase and is critical in the regulation of Nanog and Oct4
c. The random activation of genes eventually leads to the activation of endogenous Sox2 which signals the transition to the ordered phase
d. Exogenous Klf4 and c-Myc are essential for generating iPS cells and are active in the ordered phase

A

c. The random activation of genes eventually leads to the activation of endogenous Sox2 which signals the transition to the ordered phase

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31
Q 
Match the reprogramming factors to their role during the random phase
Oct4	
c-Myc	
Sox2	
Klf4

Exogenous activates gene expression (recruits chromatin remodelling complexes and binds closed chromatin)

Inhibit gene expression

Histone acetylation, exogenous Oct4 and Sox2 can bind DNA

Endogenous causes late phase (ordered). Active chromatin state and activates Oct4 and Nanog (endogenous)

A

Oct4
Exogenous activates gene expression (recruits chromatin remodelling complexes and binds closed chromatin)

c-Myc
Histone acetylation, exogenous Oct4 and Sox2 can bind DNA

Sox2
Endogenous causes late phase (ordered). Active chromatin state and activates Oct4 and Nanog (endogenous)

Klf4
Inhibit gene expression

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32
Q

How similar are human ES cell and iPS cells?

a. ES cell and iPS cells only differ in their morphology and their overall gene expression
b. iPS cells take a long time to make and ES cells require a human blastocyst to be derived from
c. iPS and ES cells have a similar morphology and surface markers but iPS cells have shorter telomeres
d. Gene and protein expression is always the same in iPS and ES cells

A

b. iPS cells take a long time to make and ES cells require a human blastocyst to be derived from

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33
Q

What is false about issues and alternative methods associated with cell transplantation therapies?

a. Viral vectors integrate randomly into the host genome, therefore insertion mutagenesis is a concern
b. RNA transcripts may trigger an immune response and often require several treatment rounds
c. Transposons like piggyback and sleeping beauty are examples of non-viral delivery methods which can be excised
d. Proteins tethered to proteins have a high efficiency but cannot facilitate transmembrane transport

A

d. Proteins tethered to proteins have a high efficiency but cannot facilitate transmembrane transport

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34
Q

What is false about the basal lamina?

a. It connect the epithelium to the stroma and is made of three layers (lamina lucida, lamina densa, reticular lamina)
b. It can aid in anchoring and structure as well as cellular processes such as migration and proliferation
c. It has ECM proteins in the form of collagens and proteoglycans only
d. Cells are usually attached via hemidesmosones

A

c. It has ECM proteins in the form of collagens and proteoglycans only

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35
Q

What can be shown by basal lamina directed gene expression in the mammary gland?

a. Mammary epithelial cells grown on plastic express cell division genes such as c-myc and cyclinD1
b. The presence of a BL encourages mammary epithelial cells to divide more and stop the expression of p21
c. When grown on BL, mammary epithelial cells lose the ability to express mammary gland specific genes like lactoferrin, casein and WAP
d. Mammary epithelial cells grown on plastic express mammary-gland specific genes such as lactoferrin and casein

A

a. Mammary epithelial cells grown on plastic express cell division genes such as c-myc and cyclinD1

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36
Q

• iPS cells demonstrate chimerism and germ line transmission but not tetraploid complementation.

A

F (show all 3)

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37
Q

• iPS cells can be generated using any differentiated cell.

A

T

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38
Q

• Exogenous Oct4 and Sox2 are essential in generating iPS cells.

A

T

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39
Q

• The stem cell niche is defined solely by location.

A

F

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40
Q

• In healthy cells (non-cancerous), proliferation and differentiation are mutually exclusive.

A

T

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41
Q

• Embryonic Germ Cells (EG) are derived from undifferentiated cells in teratocarcinoma and Embryonal Carcinoma Cells (EC) are derived from primordial germ cells (pluripotent).

A

F

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42
Q

What is not a characteristic of a malignant tumour?

a. All cells demonstrate the same, reproducible mutation
b. There are different cell populations
c. Cells can be a different state of differentiation
d. Variability is genetic and non-genetic in nature

A

a. All cells demonstrate the same, reproducible mutation

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43
Q

What best describes a theory for how tumours can develop heterogeneity?

a. The cancer stem cell theory is based on the idea that CSCs and non-CSCs can convert to one another continuously
b. The clonal evolution theory suggests that because heritable genetic and epigenetic changes are favoured in response to microenvironment pressures
c. The plastic stem cell theory suggests that Cancer cells in tumour reside in different states of stemness and differentiation
d. The cancer stem cell theory has been proved without argument

A

b. The clonal evolution theory suggests that because heritable genetic and epigenetic changes are favoured in response to microenvironment pressures

a. Plastic Stem Cell theory
c. Cancer Stem Cell Theory
d. Nope

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44
Q

What is not a feature of cancer stem cells?

a. They are tumour cells with stem cell properties
b. They are resistant to chemotherapy
c. They can drive tumour growth and metastases
d. They are easily studied due to their well-known origin and marker profile

A

d. They are easily studied due to their well-known origin and marker profile

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45
Q

What would not be found in a tumour niche?

a. Vascular network
b. Secreted factors
c. Limited stromal cells
d. Extracellular matrix

A

c. Limited stromal cells

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46
Q

How do exosomes and microvesicles compare?

a. They are the same size and density, but only exosomes use exocytosis
b. Microvesicles are much larger (100-1000nm) than exosomes (30-100nm)
c. Exosomes use blebbing whilst microvesicles use exocytosis
d. Exosomes are more dense than microvesicles

A

b. Microvesicles are much larger (100-1000nm) than exosomes (30-100nm)

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47
Q

What is true about diagnosing Pancreatic Cancer using extracellular vesicles?

a. It is not yet possible to distinguish benign from precancerous
b. The test is based on the EV membrane bound proteoglycan, GPC1
c. Glypican-1 is absent in the sera of patients with pancreatic cancer
d. Invasive sampling of the pancreatic tissue is needed to look for GPC1

A

b. The test is based on the EV membrane bound proteoglycan, GPC1

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48
Q

• Tumours are heterogeneous because they have different cell populations with different mutations, different states of differentiation, different functions and genetic and non-genetic variability.

A

T

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49
Q

• Cancer stem cells do not counteract the effect of drugs that specifically kill tumour cells.

A

F

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50
Q

• Cancer stem cells express Oct4, Sox2 and NANOG.

A

T

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51
Q

What is not a feature of an adult stem cell?

a. Self-renewal
b. Short life span
c. Multipotent
d. Found amongst differentiated cells

A

b. Short life span

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52
Q

Which is the correct order of renewal capacities?

a. liver/muscle > bone marrow > epidermis > nervous tissue
b. epidermis > bone marrow > nervous tissue > liver/muscle
c. bone marrow > epidermis > liver/muscle > nervous tissue
d. nervous tissue> liver/muscle > epidermis > bone marrow

A

c. bone marrow > epidermis > liver/muscle > nervous tissue

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53
Q

What is false about the processes underlying the fate determinants of daughter stem cells?

a. Independent choice can lead to two stem cells, terminally differentiated cell and stem cell or two terminally differentiated cells which all make up a pool of stem cells
b. Asymmetric division is influenced by determinants which localise on one side of a cell/plane
c. Haematopoietic stem cells demonstrate asymmetric division due to their reliance on the positioning of stromal cells
d. Neuroblasts commonly undergo asymmetric division

A

c. Haematopoietic stem cells demonstrate asymmetric division due to their reliance on the positioning of stromal cells

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54
Q

Which best describes an aspect of morphollaxis or epimorphosis?

a. Epimorphosis is seen in simple animals like worms and is the re-patterning and re-establishment of boundaries
b. Morphollaxis can be seen in newts and involves new growth and correct patterning
c. In morphollaxis, positional values are independent of boundary regions
d. In epimorphosis, new positional values are linked to growth from the cut surface

A

d. In epimorphosis, new positional values are linked to growth from the cut surface

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55
Q

What is false about the blastema?

a. It is made up of natural iPS cells
b. It contains de-differentiated cells in a heterogeneous collection
c. Cells cannot proliferate in it in the absence of nerve cells
d. Cells in the blastema can retain their specification even though they de-differentiate

A

a. It is made up of natural iPS cells

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56
Q

• Asymmetric division is due to a determinant on one side of a plane whilst independent choice is stochastic.

A

T

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57
Q

• Stem cells are shorter lived than all other cells in the intestine.

A

F

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58
Q

• Satellite cells are quiescent stem cells.

A

T

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59
Q

• In the Blastema, cells fully revert to pluripotency.

A

F

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60
Q

• Salamander limbs can still regenerate when nerves are damaged.

A

F

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61
Q

• nAG can bind to Prod1 and lead to limb regeneration when nerves are dysfunctional.

A

T

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62
Q

The following cannot be produced from the differentiation of neural stem cells:

a. Glia
b. Neurons
c. Hepatocytes
d. Oligodendrocytes

A

c. Hepatocytes

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63
Q

Which substrate is matched correctly with the type of neural cell it encourages the development of?

a. Fibronectin encourages growth of astrocytes and neurons
b. Laminin encourages growth of neurons and oligodendorcytes
c. Fibronectin encourages growth of neurons
d. Fibronectin encourages growth of astrocytes and oligodendrocytes

A

d. Fibronectin encourages growth of astrocytes and oligodendrocytes

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64
Q

What factors can allow neural stem cells to be maintened in culture?

a. Neural basal media, bFGF and EGF
b. Neural basal media, BMP and Noggin
c. Neural basal media, Sox2 and Oct4
d. Neural basal media, Ectodermin and Retinoic Acid

A

a. Neural basal media, bFGF and EGF

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65
Q

How can neural progenitor cells be induced?

a. Through removing Dickkopf, FGF2 and Retinoic Acid from the culture medium
b. By adding noggin to block BMP and subsequent development of extra embryonic endoderm
c. By adding Pax6, Sox1/2/3, Nestin, CD133 to drive expression of neural cells
d. By removing shh from Ventral GAD67+ neurons

A

b. By adding noggin to block BMP and subsequent development of extra embryonic endoderm

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66
Q

What is not a feature of the ventricular zone of the neural tube?

a. Extensive levels of asymmetric division
b. Absent in the adult nervous system
c. One cell layer thickness
d. Symmetric division of neuroepithelial cells (foetal neural stem cells)

A

a. Extensive levels of asymmetric division

67
Q

What is false about the subventricular zone and corticogenesis?

a. Neuroepithelial cells can give rise to radial glial cells, neuroblasts and intermediate progenitor cells
b. The stem cell niche involves progenitor and niche cells, basal lamina, axons and blood vessels
c. B cells are transit amplifying cells that give rise to A cells (neuroblast)
d. The SVZ astrocyte (B) gives rise to transit amplifying cells (C) which then give rise to neuroblasts (A)

A

c. B cells are transit amplifying cells that give rise to A cells (neuroblast) (C = TAcell)

68
Q

What is not a challenge of stem cells?

a. They difficult to isolate, but easy to purify when they are
b. In vivo integration, migration and function
c. Their ability to survive or integrate
d. Will they be tumorgenic

A

a. They difficult to isolate, but easy to purify when they are

69
Q

• Excess self-renewal can lead to tumours and excess differentiation and lead to the loss of stem cells.

A

T

70
Q

• The neuroblast contains a heterogeneous population of neural stem cells and progenitor cell types.

A

F (neurospehere)

71
Q

• Neural stem cells give rise to the most anterior regions first.

A

T

72
Q

• The addition of Shh encourages the development of ventral posterior cell types.

A

T

73
Q

• Neuroblasts migrate from the SVZ along rostral migratory stream to olfactory bulb where they differentiate into neurons.

A

T

74
Q

• Transit amplifying cells are called D cells in the SVZ and C cells in the SGV.

A

F

75
Q

• Progenitor cells can retain the ability to return to stem cells or act as stem cells when required (e.g. tissue regeneration).

A

T

76
Q

• Adult stem cells are resistant to aging because self-renewal factors from neighbouring cells in the niche increase over time.

A

F

77
Q

What best describes recent community attitudes towards stem cells in research?

a. 90% of people think it is unacceptable to use human embryonic stem cells
b. 17% of people think it is unaccapetable to use stem cells in general
c. 6% of people are unsure about using general stem cells or human ES cells
d. 88% of people are in favour of the use of human embryonic stem cells

A

c. 6% of people are unsure about using general stem cells or human ES cells

78
Q

What is involved in harvesting human ES cells?

a. IVF embryos are deliberately made in excess as supplies for stem cell research
b. Cells are derived from the inner cell mass at the 6 day stage
c. The embryo needn’t be destroyed for ES cells to be harvested
d. ES cells are derived directly from the fertilised egg on day 1

A

b. Cells are derived from the inner cell mass at the 6 day stage

79
Q

What is not a feature of stem cell use regulation in Australia?

a. Applications are considered under the Research involving Use of human embryos act 2002 and Prohibition of human cloning act 2002
b. The project is considered based on obtaining consent, likelihood of significant findings, number embryos needed
c. Once a license is received, embryos generated by human ES cells can be implanted in an animal uterus, but not human
d. Human ES stem cells may not be used but research can utilise iPS cells as an ethical alternative

A

c. Once a license is received, embryos generated by human ES cells can be implanted in an animal uterus, but not human

80
Q

What was not involved in the creation of the mouse ‘Tiny’?

a. A tetraploid blastocyst was created from somatic cell nuclear transfer
b. iPS cells were injected into a tetraploid blastocyst and fully contributed to the genetic makeup of Tiny
c. The developing embryo was implanted into a surrogate mother
d. The process was very inefficient in generating offspring

A

a. A tetraploid blastocyst was created from somatic cell nuclear transfer

81
Q

• The most stringent research restrictions apply to the use of iPS cells rather than IVF and hESC.

A

F

82
Q

What is a false statement about primordial germ cells?

a. The preserve genetic integrity and generate genetic diversity
b. Errors in differentiation can lead to infertility and cancer
c. They are the only naturally occurring totipotent cells
d. They give rise to egg and sperm and are the only cells to undergo meiosis

A

c. They are the only naturally occurring totipotent cells

83
Q

How do the different methods of specification compare?

a. European style emphasises the role of neighbouring cells
b. American style emphasises the role of ancestors and cell linage
c. Preformation emphasises the combined role of cell linage and neighbouring cells and is also referred to as European style
d. Induction is also referred to as American style and specification depends on neighbouring cells

A

d. Induction is also referred to as American style and specification depends on neighbouring cells

84
Q

Which animal specifies PGCs by induction?

a. Drosophila
b. Zebrafish
c. Mouse
d. C. elegans

A

c. Mouse

85
Q

What is the role of BMP4?

a. Activation of BLIMP1 and PRDM14 via ALK2 and SMAD signalling in mouse PGCs
b. Degradation of Retinoic Acid in the testes
c. Activation of genes for epigenetic reprogramming and somatic mesoderm in mouse PGCs
d. Allow PGC migration through the Drosophila midgut

A

a. Activation of BLIMP1 and PRDM14 via ALK2 and SMAD signalling in mouse PGCs

86
Q

What is not involved in the migration of drosophila PGCs to the gonads?

a. Germ cells are formed at the pole of the embryo
b. The cells migrate on the midgut before migrating into the mesoderm
c. The cells take 10 days to reach the gonads
d. Migration finishes with gonad coalescence

A

c. The cells take 10 days to reach the gonads

87
Q

Which molecule does not play an important role in the migration of mouse PGCs to the gonads?

a. C-kit
b. Oct4
c. Steel
d. SDF1

A

b. Oct4

88
Q

How does PGC migration in birds differ from other animals?

a. PGCs migrate along the midgut as opposed to in the blood like in mice
b. PGCs that don’t reach the gonads pose no risk of extra gonadal germ cell tumour formation
c. PGCs that don’t reach the gonads are removed by apoptosis due to the action of BAX
d. Migration is driven by interactions between steel and the c-Kit ligand

A

c. PGCs that don’t reach the gonads are removed by apoptosis due to the action of BAX

89
Q

What happens when retinoic acid is artificially increased in the testis?

a. Meiosis occurs prematurely
b. There is no response
c. CYP26B1 is downregulated
d. ALDH1A2 degrades Stra8

A

b. There is no response

90
Q

What is the role of ALDH1A2?

a. It drives retinoic acid expression in male and female mesenephros
b. It degrades retinoic acid in the testis
c. It binds to Stra8 to initiate meiosis
d. It influences testis development

A

a. It drives retinoic acid expression in male and female mesenephros

91
Q

What is false about GDNF (glial cell-line derived neurotrophic factor) ?

a. It is a member of the TGFB superfamily
b. It is secreted by sertoli cells
c. It is expressed strongly in the ovary
d. It is critical for the survival and self-renewal of SSCs

A

c. It is expressed strongly in the ovary

92
Q

What is not a feature of LGR5?

a. It is a marker on ovarian somatic stem cells and adult stem cells such as those of the colon and small intestine
b. It is a WNT target gene and G-protein-coupled-receptor for R-spondins
c. It is upregulated in some cancers
d. It is found exclusively on ovarian somatic stem cells and testis somatic stem cells

A

d. It is found exclusively on ovarian somatic stem cells and testis somatic stem cells

93
Q

• Germline cells are segregated from somatic cells during development and not from oocyte in the specification of mouse PGCs.

A

T

94
Q

• The most critical molecule for PGC specification in the mouse is BMP4.

A

T

95
Q

• The C-kit ligand can be mutated to increase the amount of PGCs that reach the gonads.

A

F

96
Q

• Mouse germ cells migrate much faster than drosophila germ cells.

A

F

97
Q

• During differentiation of PGCs, the Sex genotype decides if the genital ridge becomes testis or ovary and this environment determines if germ cells differentiate.

A

T

98
Q

• If XY PGCs are put in the ovary, they develop as oocytes.

A

T

99
Q

• Spermatogonium enter meiosis before birth and Oogonium enter meiosis post natally.

A

F

100
Q

• Ovary germ cells enter meiosis in embryogenesis and arrest in prophase 1. Male germ cells enter meiotic arrest until puberty.

A

T

101
Q

• The Spermatogonial Stem Cell niche is aided by tight junctions that form the blood testis barrier.

A

T

102
Q

• Somatic stem cells can be found in both the ovaries and testis.

A

F (ovary)

103
Q

What is false about X inactivation and epigenetics?

a. A XXX female will have 3 barr bodies.
b. Changes are due to gene expression and not DNA sequence
c. Changes can be preserved through multiple cell divisions
d. A random X chromosome is inactivated in each cell of the embryo

A

a. A XXX female will have 3 barr bodies. (2)

104
Q

What can methylation NOT lead to?

a. The recruitment of factors that modify histones
b. Nucleosomes forming tight complexes with DNA to block transcription factor binding
c. Gene activation at AT rich regions
d. The ability to differentiate a newly synthesised DNA strand from it’s template

A

c. Gene activation at AT rich regions

105
Q

How do RNA polymerase and transcription factors access DNA?

a. When they are highly condensed as 30nm fibres
b. Following methylation of histone tails which decondenses nucleosomes
c. When the histone tails are cleaved by a transcription protease
d. Following acetylation which uncondenses nucleosomes

A

d. Following acetylation which uncondenses nucleosomes

106
Q

What happens following the modification of histone tails?

a. The state of chromatin compaction is affected
b. Binding sites for chromatin modifying proteins are blocked
c. Polycomb protein is expressed ubiquitously
d. The methylation site is always phosphorylated

A

a. The state of chromatin compaction is affected

107
Q

What is false about Polycomb protein?

a. It binds H3Me3K27
b. It is part of a polycomb repressor complex
c. It acts to enhance transcription
d. It maintains the repression of hox gene expression in specific developing body segments

A

c. It acts to enhance transcription

108
Q

What is involved in the developmental consequences of DNA methylation?

a. In X chromosome inactivation, the inactive chromosome is not inherited
b. Genomic imprinting follows mendelian rules
c. Imprinting is due to differential methylation
d. Female germ cells are remethylated during meiosis in the embryonic gonad

A

c. Imprinting is due to differential methylation

109
Q

How does insulin-like growth factor 2 demonstrate imprinting?

a. WT sperm and mutant Igf2 eggs produce small offspring
b. Mutant Igf2 sperm and WT eggs produce normal offspring
c. It is expressed from the female chromosome
d. Small offspring are produced from Igf2 mutant sperm and WT eggs

A

d. Small offspring are produced from Igf2 mutant sperm and WT eggs

110
Q

What plays a role in considering if IPS cells have similar epigenomes to ES cells?

a. iPS cells must erase all methylation marks to revert to pluripotency
b. ES and iPS cells have exacly the same methylation patterns
c. The reversion process leads to non-random methylation events
d. Somatic memory is unique to ES cells that have been methylated

A

a. iPS cells must erase all methylation marks to revert to pluripotency

111
Q

• Methylation of cytosines only occurs when they are followed by G.

A

T

112
Q

• DNA methylation can lead to accidental expression of inappropriate genes.

A

F

113
Q

• MeCP2 directly binds methylated Cs and recruits histone deaceytlase, methyltransferase and Dnmt3.

A

T

114
Q

• Chromosomes are most highly condensed and visible during metaphase.

A

T

115
Q

• Genes expressed in stem cells do not play a role in cell proliferation or housekeeping.

A

F

116
Q

• A Deletion of a small region of the long arm of chromosome 15 can lead to Prader-willi syndrome when inherited from the egg and Angelman syndrome when inherited from the sperm.

A

F

117
Q

What doesn’t have a role in allowing epigenetic changes to be heritable?

a. The passive process of DNA replication
b. TET proteins can actively reverse methylation
c. DNMT1 recognises hemi-methylated DNA and methylates the non-methylated strand
d. TET proteins only de-methylate DNA at restricted points during development

A

a. The passive process of DNA replication (reversibility)

118
Q

How can a cancer cell differ to a normal cell in its DNA methylation patterns?

a. CpG islands undergo extensive de-methylation
b. The repetitive elements are methylated
c. There can be genome-wide hypo-methylation at CpG laden promoters
d. Hyper-methylation can occur at CpG islands and imprint control regions

A

d. Hyper-methylation can occur at CpG islands and imprint control regions

119
Q

What is the significance of CpG island hyper-methylation?

a. DNA methylation is an alternative to genetic mutation that can silence oncogenes to encourage tumour formation
b. When it occurs at imprint control regions, a loss of imprinting and overexpression of imprinted growth control genes can occur
c. The same CGIs are hyper-methylated in all tumour types which aids diagnosis
d. The methylation pattern is easily distinguished from that which occurs during the natural aging process

A

b. When it occurs at imprint control regions, a loss of imprinting and overexpression of imprinted growth control genes can occur

120
Q

Which is a well-known example of CGI methylation of a single gene resulting in cancer?

a. BRCA1 and colorectal cancer
b. MGMT and gliomas
c. MLH1 and retinoblastoma
d. RB and breast cancer

A

b. MGMT and gliomas

121
Q

What is untrue about using hyper-methylated genes as biomarkers?

a. They can be used as biomarkers because CGI are usually un-methylated
b. They can be used to discriminate tumour from normal tissue for diagnosis
c. They can influence treatment strategy
d. They can only be used as biomarkers for imprint control regions as CGI are usually methylated

A

d. They can only be used as biomarkers for imprint control regions as CGI are usually methylated

122
Q

What is a feature of bivalent genes in stem cells?

a. H3K27me3 marks the gene as repressed and is mediated by PRC2
b. RNA pol II is always active
c. The genes are active but poised for an enhancement in expression
d. H3K4me3 marks the gene as repressed and is mediated by MLL

A

a. H3K27me3 marks the gene as repressed and is mediated by PRC2

123
Q

What is a feature of bivalent genes in cancer stem cells?

a. They are hypo-methylated
b. There is an absence of H3K4me3 and H3K27me3 marks
c. Genes are no longer poised for activation and are instead stably activated
d. RNA pol II is paused at the promoter and bound by PRC2 and MLL

A

b. There is an absence of H3K4me3 and H3K27me3 marks

124
Q

What is a feature of genome-wide hypo-methylation?

a. When it occurs in CpG poor promoters, oncogenes can be repressed
b. When it occurs in imprint control regions, imprinting can be enhanced
c. Genomic instability can occur when it happens in repeat or intergenic regions
d. It is only seen in some tumours and depends largely on location

A

c. Genomic instability can occur when it happens in repeat or intergenic regions

125
Q

What is a feature of cancer stem cells?

a. They are often successfully targeted during chemotherapy
b. They are found in homogenous tumours
c. They can self-renew or differentiate like normal stem cells
d. They are not influenced by epigenetic effects

A

c. They can self-renew or differentiate like normal stem cells

126
Q

What is a consideration of the CSC theory?

a. Whether self-renewal arise in the original stem cell or did the CSC attain it during tumorigenesis
b. CSCs can be found in all cancers
c. CSC theory cannot co-exist with genetic heterogeneity and clonal evolution
d. Unlike cancer, the proportion and features of CSCs do not change over time

A

a. Whether self-renewal arise in the original stem cell or did the CSC attain it during tumorigenesis

127
Q

How does normal and tumour cell differentiation compare?

a. Self-renewal can be imparted on normal stem, progenitor or differentiated cells following genetic or epigenetic changes
b. The stem cell is always the cell of origin for differentiated tumour cells
c. Differentiation is irreversible in normal cells but not tumour cells
d. Differentiated tumour cells still have the capacity to self-renew

A

d. Differentiated tumour cells still have the capacity to self-renew

128
Q

What encourages the self-renewal of CSCs?

a. DNA is hypo-methylated in cancer rather than poised for activation/repression
b. DNA methylation is less stable because there is up regulation of de-methylating (TET) enzymes
c. DNA methylation makes it more difficult to activate developmental genes and differentiation is discouraged
d. Epigenetic changes enforce differentiation and self-renewal in a reversible manner like genetic changes

A

c. DNA methylation makes it more difficult to activate developmental genes and differentiation is discouraged

129
Q

• CpG island methylation increases as the tumour advances.

A

T

130
Q

• Hyper-methylated genes are enriched for genes silenced by polycomb repressive complex 2 in embryonic and adult stem cells.

A

T

131
Q

• Hypo-methylation of imprint control regions can lead to open chromatin and illegitimate recombination as well as transcriptional activation of repeats and transposition.

A

F (repeats, intergenic regions)

132
Q

• Tumours driven by tumour suppresser hyper-methylation show enhanced tumorigenesis following the depletion of DNA methylation.

A

F

133
Q

• Genetic alteration of epigenetic modifiers can lead to epigenetic effects and epigenetic effects can result in genomic instability.

A

T

134
Q

• The most common drugs that target epigenetic machinery are aimed at chromatin remodelling proteins.

A

F (DNMT)

135
Q

• Tumour heterogeneity is driven by genetic changes but not epigenetic changes.

A

F

136
Q

• In CSCs, epigenetic changes cannot impart self-renewal capacities.

A

F

137
Q

• In CSCs, transmitted epigenetic changes can lead to the maintenance of the stem cell state at the expense of differentiation.

A

T

138
Q

• Using DNA methyltransferase inhibition to deplete DNA methylation at bivalent genes could be used to remodel the CSC epigenome and treat cancer.

A

T

139
Q

What is not a property of a pluripotent stem cell?

a. Grows indefinitely in vitro
b. Maintains normal genetic makeup
c. Can differentiate into a range of somatic and extra embryonic tissue in vivo
d. Can colonise all tissue except that of the germ line

A

d. Can colonise all tissue except that of the germ line

140
Q

What is not a practical application of iPSC?

a. Reprogramming blood cells of someone with liver disease to form hepatocytes
b. Screening induced cells to make disease and patient specific drugs
c. Creating human embryos without the need for a uterus
d. Implanting hepatocytes with corrected gene mutations into a patient with liver disease

A

c. Creating human embryos without the need for a uterus

141
Q

What is not an advantage of iPSC?

a. Material and technology is readily accessed
b. Complex multigenic diseases can be modelled in vitro and in vivo
c. Individual variations in tissue regeneration and repair pathways can be examined and biomarkes can be developed
d. Unlike ESC, the effects of a single gene mutation on different genetic backgrounds can be analysed

A

b. Complex multigenic diseases can be modelled in vitro and in vivo (in vitro)

142
Q

What is a consideration when using iPSC?

a. The gene must be delivered in a viral vector that integrates into the host genome to ensure full efficiency and safety
b. There are variations in differentiation capacity for ES and iPS cells in culture
c. The type of cell used to give rise to iPSC should be chosen carefully as stem cells lack somatic tissue memory
d. Genetic lesions and chromosome aberrations can only be observed in hESCS

A

b. There are variations in differentiation capacity for ES and iPS cells in culture

143
Q

What would not be observed as a result of variation in differentiation capacity of pluripotent cells?

a. Variation in TALEN cleavage sites
b. Transcriptional variation
c. Variation in differentiation efficiency
d. Disease variation in contributing to phenotype

A

a. Variation in TALEN cleavage sites

144
Q

What is a way for genetic lesions to arise during the development of pluripotent stem cells?

a. The somatic origin of an iPSC will not influence genetic lesions
b. iPSCs can develop aberrations due to their somatic origin, the reprogramming process and culture conditions
c. iPSCs are resistant to aberrations that could arise in cell culture
d. hESCs can develop aberrations during the induced reprogramming stage

A

b. iPSCs can develop aberrations due to their somatic origin, the reprogramming process and culture conditions

145
Q

How do ESC and iPSC compare?

a. They have different gene expression patterns
b. They show varying degrees of susceptibility to genetic change
c. They have similar patterns of DNA methylation and histone modification
d. They have a similar capacity for differentiating into specific linages

A

c. They have similar patterns of DNA methylation and histone modification

146
Q

• ESCs are the only kinds of human pluripotent stem cells.

A

F (iPS)

147
Q

• iPS cells can be used to create cardiomyocytes of people with long Q-T syndrome and demonstrate how their heart beat rhythm is affected and influenced by drugs.

A

T

148
Q

• Cell replacement of neurons is more critical than enhancing plasticity.

A

F

149
Q

• TALENS are simpler to make and more efficient than CRISPR.

A

F

150
Q

• TALEN endonucleases can be used to genetically manipulate human pluripotent stem cells.

A

T

151
Q

• Most ES cell lines are very unstable.

A

F

152
Q

• It may be possible to make germline modifications in humans and produce iPS cell gametes

A

T

153
Q

What is not a challenge for stem cell therapy?

a. Safety due to the possibility of tumour formation
b. Delivery method and which cell to use
c. Funding and business models
d. Finding enough donor embryos to harvest ESCs

A

d. Finding enough donor embryos to harvest ESCs

154
Q

What is involved in the framework of stem cell product development in Japan?

a. The main goal is to bridge the valley of death
b. Clinical trials in mice occur after marketing
c. After safety has been established, a marketing stage occurs and patients can be recruited
d. There is no marketing stage and the process is streamlined

A

c. After safety has been established, a marketing stage occurs and patients can be recruited

155
Q

What is not involved in forming neural tissue in vitro?

a. Embryonic heads are treated with noggin
b. Resulting neural tissue secretes Sox2 and noggin
c. Primitive neural tissue is marked by nestin and Sox2
d. The eye forms as an outgrowth of the embryonic brain

A

b. Resulting neural tissue secretes Sox2 and noggin

156
Q

Why is macular degeneration a promosing target for stem cell therapy?

a. Many cells are required to replace the tissue
b. The epithelium is functional when derived from ES cells
c. The eye is accessible despite being difficult to image
d. There is no requirement for immunosuppression

A

b. The epithelium is functional when derived from ES cells

157
Q

Which is not a clinical trial for pluripotent stem cell therapy?

a. Breast cancer
b. Type 1 diabetes
c. Parkinson’s disease
d. Spinal cord injury

A

a. Breast cancer

158
Q

What is a consideration for using iPS stem cell therapy?

a. Reprogramming to pluripotency is always complete
b. Genetic lesions cannot occur from iPS cells
c. Differentiation capacity can vary between cells
d. Tumour formation can only arise from bone marrow derived iPSC

A

c. Differentiation capacity can vary between cells

159
Q

What is an issue for the regulation of stem cell therapies?

a. Cell therapies have a short half life
b. Risk benefit assessment is critical
c. Treatment requires a small dose of specifically designed cells
d. The main focus for therapy should be how much profit can be gained

A

b. Risk benefit assessment is critical

160
Q

What is not a feature of unfounded stem cell therapies (i.e. stem cell clinics) ?

a. They can successfully cure metabolic diseases
b. Treatments are often costly
c. Treatment lacks scientific rational
d. Evidence for treatment is anecdotal

A

a. They can successfully cure metabolic diseases

161
Q

• In the past 10 years there have been about 2500 clinical trials and 50% are in phase 2-3.

A

T

162
Q

• To prevent mitochondrial disease, the egg of a mum with mitochondrial disease can receive exogenous DNA before being fertilised with the fathers sperm.

A

F (need maternal DNA and donor egg. Egg has mtDNA)

163
Q

• Chromosomal changes in ESC and iPSC are not similar to those changes shown by cancer.

A

F

164
Q

Why is Lgr5 found on many stem cells?

a. It promotes asymmetric division
b. It is a Wnt receptor
c. It’s absence always leads to cancer
d. It interacts with integrin to anchor Stem Cells in their niche

A

b. It is a Wnt receptor

CEDB30004 Stem Cells in Development and Regeneration (18 decks)

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