Mechanisms of Stem Cell Renewal and Cancer. Flashcards
(134 cards)
1
Q
Define a blastocyst?
A
A hollow ball of cells that is derived from a fertilised egg.
2
Q
Define oligopotent stem cells?
A
A type of stem cell that lies between a multipotent stem cell and a unipotent stem cell.
3
Q
Define potency in relation to stem cells?
A
The ability of a stem cell to divide and differentiate, but it is much more specific than a stem cell.
4
Q
Define a progenitor cell?
A
A type of cell that can differentiate, but has less potency than a stem cell.
5
Q
Define regenerative medicine?
A
The use of stem cells to replace damaged tissue.
6
Q
Define satellite cells?
A
Pre-cursors to muscle cells.
7
Q
Define cell self-renewal?
A
An ability that stem cell have which allows them to identical undifferentiated daughter cells.
8
Q
Define a zygote?
A
A fertilised egg cell.
9
Q
What are stem cells?
A
Undifferentiated cells that have the ability to self-renew via cell division and can develop into any cell in the body.
10
Q
How can stem cells repair a damaged tissue in the body?
A
They can differentiate into that tissue and repair the damage.
11
Q
Can stem cells perform specialised tasks within the body?
A
Because stem cells are unspecialised it means that they cannot form specific tasks in the body.
12
Q
Why are stem cells increasingly becoming a part of modern medicine?
A
Because of their ability generate healthy cells that can be used to replace cells that have been affected by disease.
13
Q
What is a common method of using stem cells to cure a disease?
A
Forcing stem cells to become certain cells.
These cells are then grown in the lab and then inserted into the patient.
14
Q
How can stem cells be used in drug research?
A
Scientists can force stem cells to form a certain tissue which they can then use to test drugs on.
15
Q
What are the 3 types of stem cells that can be injected into a patient?
A
Undifferentiated or partly differentiated stem cells.
Differentiated stem cells.
Injection of certain factors into stem cells.
16
Q
How are undifferentiated stem cells usually inserted into a patient?
A
Via intravenous injection or via a direct injection into the target tissue.
17
Q
How are differentiated stem cells usually inserted into a patient?
A
These cells have been differentiated into specialised cells ex vivo and are then injected into the target tissue.
18
Q
What is the injection stem cells that contain certain factors?
A
The injection of stem cells that contain drugs or certain factors such as growth factors.
19
Q
Why are stem cells that contain certain factors injected into the body?
A
To stimulate the synthesis of endogenous stem cells so that the body can produce it own stem cells.
20
Q
What are the 4 types of stem cell potency?
A
Totipotent stem cells.
Pluripotent stem cells.
Multipotent stem cells.
Unipotent stem cells.
21
Q
What are totipotent stem cells?
A
Stem cells that can develop into any cell in the body, including placental tissues.
22
Q
What kind of stem cells could be used to form an entire organism autonomously?
A
Totipotent stem cells.
23
Q
What are pluripotent stem cells?
A
Stem cells that can become any cell within the 3 embryonic germ layers.
24
Q
What kind of cells can pluripotent stem cells form?
A
Almost any cell within the body, including germ cells, but they cannot form the cells of the placenta.
25
What are multipotent stem cells?
Stem cells that have the ability to generate a variety of cells that can be found within a particular tissue or organ.
26
What is an example of a multipotent stem cell?
A haematopoietic stem cell which can be come a red blood cell, a white blood cell or a platelet protein.
27
What are unipotent stem cells?
Stem cells that can only form one type of cell.
E.g. A spermatogonial stem cell can only form a sperm cell.
28
What are the 3 major types of stem cell?
Embryonic stem cells.
Adult or somatic stem cells.
iPSC’s (induced pluripotent stem cells).
29
What are embryonic stem cells?
Stem cells that are derived from the inner cell mass of a blastocyst before the 3 germ layers have been formed.
30
What kind of cells can embryonic stem cells form?
They can become any cell within the human body, except for the placenta and umbilical cord.
31
Embryonic stem cells have what level of potency?
Pluripotency.
32
What are adult or somatic stem cells?
Undifferentiated stem cells that are found in specific locations within mature tissues.
33
Adult stem cells have what level of potency?
They are multipotent.
34
Are adult stem cells more specialised than embryonic stem cells?
Yes, as they can only generate cell types for the specific tissue or organ that they are located in.
35
What are iPSC’s (induced pluripotent stem cells)?
Lab engineered stem cells that are made by converting tissue specific cells into cells that behave like embryonic stem cells.
36
What kind of stem cells have helped scientists learn about disease progression within certain tissues?
iPSC's.
37
What is stem cell self-renewal?
The process by which stem cells divide and make more stem cells.
38
How long does stem cell self-renewal last for?
Throughout an organisms lifetime.
39
What are the 2 methods that stem cells can divide?
Asymmetric cell division.
Symmetrical stem cell division.
40
What is asymmetric stem cell division?
A type of cell division that produces 2 daughter cells.
41
What are the characteristics of the daughter cells that are produced by asymmetric cell divsion?
One of the daughter cells is identical to the parent cell and the other is a progenitor or differentiated cell.
42
Does asymmetric division increase the population of stem cells?
No.
43
What is symmetic stem cell division?
This type of cell division produces 2 daughter cells that are each identical to the parent cell.
44
Does symmetric division increase the population of stem cells?
Yes.
45
Why is stem cell renewal important in an organsim?
It allows stem cells to increase their population during the development of an organism.
It allows for stem cells to maintain their population within an adult so they can be used for the repair of tissues.
46
Any defects in stem cell renewal can lead to what?
Developmental defects and premature ageing, as well as cancer in certain tissues.
47
An understanding of the self renewal mechanisms of stem cells can give us an understanding about what?
The processes of development, ageing and the onset of cancer.
48
The intrinsic mechanisms that are used during the division of stem cells are found where?
Inside the stem cell.
49
What are the intrinsic factors that are used during the division of stem cells made up of?
Proteins.
50
What happens to the intrinsic factors inside a stem cell if it divides symetrically?
The intrinsic proteins will be equally shared between the 2 daughter cells.
51
What happens to the intrinsic factors inside a stem cell if it divides asymetrically?
The proteins are distributed unequally and this is why asymmetric division results in 2 different daughter cells.
52
How are intrinsic factors placed into the 2 daughter cells during asymetic division?
The apical (larger) daughter cell inherits self renewal promoting factors that allow it to remain identical to its parent.
The smaller basal cell receives differentiation factors and this is why it is different from the parent cell.
53
What controles the fate of the daughter cells during asymmetric cell division?
The distribution of the cellular contents of the parent cell.
54
Where are the extrinsic mechanisms of cell division located?
Factors that are outside of the cell.
55
What regulates the intrinsic factors of cell division?
The extrinsic factors.
56
What is the common extrinsic factor that affects stem cell division?
The microenvironment or niche that the stem cell is in.
57
What are the specific niches that stem cells are in?
They contain specialised cells canlled niche cells which promote stem cell maintenance and stem cell function.
58
What are niche cells capable of?
They can provide an anchorage site for stem cells.
They can produce certain signals that regulate stem cell survival and differentiation.
59
What happens if a stem cell is removed from its niche?
It will remain undifferentiated as they will not receive the signal to divide.
60
How do niche cells affect asymmetic cell division?
In assymetric tem cell division, the cell that is in contact with the cell niche retains its undifferentiated status.
The other cell that is formed is not in contact with the niche and it will be differentiated.
61
What are the 3 specific networks that are invovled in stem cell self renewal programs?
Balancing proto-oncogenes.
Gate keeping tumour suppressors.
Care taking tumour suppressors.
62
How will proto-oncogenes affect stem cell self renewal?
They promote self renewal.
63
How will gate keeping tumour suppressors affect stem cell self renewal?
By limiting self renewal.
64
How will care taking tumour suppressors affect stem cell self renewal?
By maintaining genomic integrity.
65
Why is it important that there is a balance between proto-oncogenes and tumour suppressors?
As too many proto-oncogenes would result in undifferentiated stem cell formation.
Too many tumour suppressors would result in too few stem cells.
66
Why must stem cell proliferation constantly changing over time?
Tissue is constantly changing over time due to ageing and stem cells must keep up with and respond to these changes.
67
How has stem cell renewal responded to tissue changes that occur with ageing?
They have different self renewal programs at different stages of life.
68
What do the different stem cell self renewal programs depend on as the body age's?
They depend on transcriptional regulators which are shared between stem cells and change between different stem cells at different stages of life.
69
What is the function of the tumour suppressors P16 (INK-4a) and P19 (ARF)?
They prevent stem cells from self renewing.
70
How do the tumour suppressors P16 (INK-4a) and P19 (ARF) prevent stem cells from self renewing?
Through the use of overlapping transcriptional regulators whose expression and function change with age.
71
How does the expression of the tumour suppressors P16 (INK-4a) and P19 (ARF) change over a stem cells lifetime?
As an individual stem cell ages the expression of P16 (INK-4a) and P19 (ARF) is increased.
72
What happens when the expression of the tumour suppressors P16 (INK-4a) and P19 (ARF) is increased within an ageing stem cell?
It reduces the ability of the stem cell to renew and reduces the risk of cancer.
73
Why can the elderly not renew stem cells as easily as young people?
Because of the higher expression of the tumour suppressors P16 (INK-4a) and P19 (ARF).
74
How does ageing affect the regenerative capacity of stem cells?
Age is associated with a reduction in the regenerative capacity of stem cells.
75
What will accumulate if stem cell regeneration is compromised?
Unrepaired or damaged tissues.
76
Are the stem cell niches affected by ageing?
Yes.
77
What causes the changes in regenerative capacity of stem cells as people age?
Changes in the self renewal programs that are related to tumour suppression.
78
What are 2 sets of stem cells that do not decline with age?
Satellite cells and haematopoietic stem cell (HSC’s).
79
What features of HSC's and satellite cells do decline with age?
Their functional properties.
80
What affects a satellite cells ability to differentiate into a muscle cell in an elderly person?
The ability of these cells to proliferate and respond to an injury is severely affected by ageing to their local niches.
81
Are old muscle cells capable of proliferating?
Yes, but this proliferation process is reduced because of the ageing niche.
82
What happens when old muscle cells are put into a young niche?
They can proliferate.
83
What happens when young muscle cells are put into an old niche?
It cannot regenerate.
84
What affects an HSC's ability to differentiate into a muscle cell in an elderly person?
The functional properties of HSC’s do decline with age and the niche has no influence over this decline.
85
Are old HSC stem cells capable of regenerating?
No.
86
What happens if an old HSC is placed in a young niche?
They cannot regenerate.
87
What happens if a young HSC is placed in an old niche?
They can regenerate,
88
How do normal stem cells usually divide?
Asymmetrically and this gives rise to stem cells and progenitor cells.
89
Why do normal stem cells tend to divide asymmetrically?
Due to the P-53 dependent regulation of the protein C-MYC.
90
What protein ensures that self renewal is maintained in stem cells?
P21.
91
How many divisions will each stem cell normally perform?
Around 6 or 7 divisions.
92
What happens to the P53 regulation of stem cell division in cancer cells?
P53 is inactive and C-MYC proteins is up-regulated.
This leads to the symmetric division allowing for the proliferation of stem cells.
93
What happens to the P21 regulation of stem cell division in cancer cells?
It up-regulated and this enhances stem cell self-renewal abilities, leading to increased proliferation of cancerous stem cells.
94
What does the increased proliferation of cancerous stem cells eventually form?
A tumour.
95
What are the 3 abilities that cancerous stem cells have in people?
The ability to generate a xenograft.
The ability to be serially transplanted into a xenograft assay and self renew.
The ability to generate daughter cells that possess some proliferative capacity, but are unable to initiate the cancer.
96
What is a xenograft?
A tissue which histologically resembles the parent tumour from which it was derived.
97
What are the 4 pathways that help to guide the self renewal of cancer cells?
The WNT pathway.
The NOTCH pathway.
The HEDGEHOG pathway.
The B cell specific Moloney murine leukaemia virus site (BMI-1) pathway.
98
What does the activation of any of the 4 pathways that guide the self renewal of cancer cells lead to?
It allows for cancer cells to develop and proliferate uncontrollably.
99
Must cancer cells follow the 4 pathways that guide the self renewal of cancer cells in order to divide?
They can bypass these pathways and find alternative pathways that allow them to continue to divide.
100
Will the microenvironment affect the ability of cancer cells to self renew?
Yes.
101
What does the WNT pathway usually signal for?
It is an ancient developmental pathway that controls stem cells and cellular fate during development.
102
What proteins are formed from the WNT pathway?
The WNT pathway codes for the WNT family which is a group of around 19 different glycoproteins.
103
What happens when the WNT pathway is de-activated?
A group of proteins will bind to beta-catenin and phosphorylate it.
This marks the beta-catenin molecule for ubiquitination and it is eventually destroyed.
104
What happens when the WNT pathway is activated?
A WNT protein binds to the frizzled protein and this attracts the protein complex that usually binds to beta-catenin.
This means that beta-catenin is not degraded and it will bind to the WNT gene and activate it.
105
What happens when WNT pathway is activated, after beta catenin has bound to the WNT gene?
The WNT gene is activated it stimulates the division of stem cells.
106
What happens if the WNT gene is permanently activated?
There is uncontrolled cell division.
107
The malfunction of the WNT pathway is often seen in what cancer in humans?
Colon cancer.
108
What does the NOTCH pathway usually do?
It involves ligand/receptor interactions between neighbouring cells.
109
What is the name of the receptor that is used in the NOTCH pathway?
The NOTCH receptor.
110
What usually happens when the ligand binds to the NOTCH receptor?
The NICD is cleaved and it will be translocated into the cells nucleus where it can lead to gene expression.
111
How is the NOTCH receptor usually arranged on the cell membrane?
It is located partly out of the cell and partly in the cell.
112
What is the name of the part of the NOTCH receptor that is located inside the cell?
As the NICD.
113
What happens if there is a mutation on the ligand or receptor of the NOTCH receptor?
The interaction between ligand and receptor may not take place.
Some mutations lead to excess activity in the receptor meaning the NICD can overstimulate gene expression.
114
What are the 4 different NOTCH receptors that are found in mammals?
NOTCH 1.
NOTCH 2.
NOTCH 3.
NOTCH 4.
115
What is the HEDGEHOG protein?
A 400-460 amino acid precursor protein.
116
What is special about the terminal N domain of the HEDGEHOG protein?
It works as a signalling molecule.
117
What is special about the terminal carboxyl group of the HEDGEHOG protein?
It contains an auto catalysing molecule.
118
What does the HEDGEHOG pathway usually code for?
For controlling cell growth, tissue patterning and morphogenesis in the developing animal.
119
Why are HEDGEHOG proteins expressed in adulthood?
For the maintenance and proliferation of stem cells.
120
What proteins are affected by the HEDGEHOG protein?
PATCHED and SMOOTHENED.
121
Where are the PATCHED and SMOOTHENED proteins located?
They lie next to each other.
122
How does the proximity of PATCHED to SMOOTHENED affect intracellular signalling?
They repress intracellular signalling in SMOOTHENED and this prevents it from activating intracellular targets.
123
What happens when the HEDGEHOG protein binds to the PATCHED protein?
It breaks the inhibition of PATCHED and allows for intracellular signalling within SMOOTHENED to take place.
124
What happens when the intracellular signalling within SMOOTHENED takes place?
It allows for the self renewal of stem cells.
125
What happens if the HEDGEHOG pathway malfunctions?
The HEDGEHOG protein permanently binds to PATCHED and the SMOOTHENED protein is activated indefinitely.
126
What happens if the SMOOTHENED protein is activated indefinitely?
It can lead to the constant proliferation of stem cells.
127
What is the BMI-1 pathway usually involved in?
In the differentiation and self renewal of stem cells.
128
What proteins are produced by the BMI pathway?
A group of proteins that are known as the polycomb proteins.
129
What is the function of the polycomb proteins?
They are well known epigenetic silencers that target the P-16 and P-19-ARF locus.
130
What are the P-16 and P-19-ARF locus responsible for?
For suppressing stem cell proliferation.
131
What happens if the proteins that are produced by the BMI-1 pathway are excessively active?
They will suppress P-16 and P-19-ARF and this leads to excess proliferation of stem cells.
132
The over-expression of BMI-1 proteins is critical in what process?
In the maintenance of CSC’s in human tissue.
133
The over-expression of BMI-1 proteins is highly up-regulated in what cancers?
In cancers of the lung, breast and neuroblastoma.
134
What is potential way of preventing the accumulation of CSC's?
The inhibition of a certain step in any of the cancerous pathways.
