Stem Cells & Cancer Flashcards
1
Q
what happens to a fertilized egg during development
A
it will repeatedly divide leading to the formation of a complex multicellular organism
2
Q
what is totipotency
A
the ability of one cell to divide and produce all differentiated cell types in an organism
3
Q
totipotency is orchestrated by what
A
the genome
4
Q
what is an example of totipotency
A
a fertilized egg
5
Q
what tissue is skin composed of
A
- epithelial
- connective
- (each dermal tissue differs in compositions of cell type/ proteins etc)
6
Q
what 3 factors contribute to stability of tissue renewal
A
- cell communication
- selective cell adhesion
- cell memory
7
Q
label which layers are which
A
8
Q
after a cell becomes specialized, will their future divisions follow that specialization, or can it continue to specialize in different manners
A
- future divisions will only produce cells of the same variety
9
Q
a proliferating cell relies on what to maintain its idenitty
A
cell memory
10
Q
how do proliferating cells maintain their identity
A
patterns of gene expression are passed onto daughter cells
11
Q
how do cells facilitate memory
A
- many ways, including:
- activation of master transcription regulators (typically results in a positive feedback loop)
- DNA methylation (methylation of C residues which attract proteins that inhibit transcription)
12
Q
describe how master transcription regulators work
A
- a protein will not be made because it is required for the transcription of its own gene
- a transient signal turns on the expression of the gene
- the gene will then continue to be transcribed in absence of the initial signal
- (signal will produce a little bit of A which, which turns on gene A, producing lots of A, positive feedback loop producing more A)
13
Q
can most specialized, differentiated cells that need replacement divide
A
most are unable to divide (terminally differentiated)
14
Q
what are terminally differentiated cell examples
A
- RBC
- superficial epidermal cells
15
Q
cells that replace terminally differentiated cells are generated by what
A
from a stock of proliferating precursor cells
16
Q
where are precursor cells derived from
A
a smaller pool of stem cells that are not differentiated and can divide without limit
17
Q
where are precursor and stem cells typically retained
A
typically retained in resident tissues along w their differentiated progeny
18
Q
what allows differentiation in precursor and stem cells
A
transcription regulations
19
Q
describe the pathway of stem cell to terminally differentiated cells
A
- stem cell
- precursor cell
- proliferating precursor cells
- terminally differentiated cells
20
Q
describe the structure of the small intestine
A
- comprised of absorptive and secretory cells arranged as simple epithelium
- tissues includes crypts which descend into the underlying connective tissues
- stem cells are near the bottom of the crypt
- stem cells give rise to precursor cells which move upwards
- precursor cells differentiate as they move upwards until they reach the tip, where they are shed into the gut lumen
21
Q
describe the structure of of the epidermis
A
- stratified epithelium
- proliferating stem cells and precursor cells are confined to the basal layer, adhered to the basal lamina
- differentiating cells travel outwards and the terminal ones shed from the surface
22
Q
can a single type of stem cell give rise to several types of differentiated progeny
A
oftenly yes
23
Q
what is hematopoiesis
A
blood formation
24
Q
what is an example of stem cells giving rise to several types of differentiated progeny
A
- hematopoiesis
- all types of blood cells originate from hematopoietic stem cells found in the bone marrow
25
how are stem-cell systems controlled
- extracellular signals exchanged between stem cells
- stem cell progeny
- other cell types as well as the intracellular signaling pathways they activate
26
how is intestinal stem cell system control mediated
Wnt proteins
27
what do Wnt proteins do (broadly)
promote the proliferation of stem cells and precursor cells at the base of each intestinal crypt
28
what produces signals to prevent the activation of the Wnt pathway outside the crypt
cells in the crypt
29
what kind of signals do cells in the crypt produce
- signals to prevent the activation of the Wnt pathway outside the crypt
- diversification signals to ensure some cells differentiate into secretory cells while others become absorptive cells
30
what does the Wnt pathway maintain
the proliferation of stem cells and precursor cells in intestinal crypts
31
what happens in the absence of Wnt signaling
the adenomatous polyposis coli (APC)- containing complex degrades the signal molecule beta-catenin
32
what happens in the presence of Wnt signaling
the APC containing complex is inactivated leading to the transcription of genes that promote the proliferation of stem cells and precursor cells
33
what enables continuous renewal and repair of their designated tissues
stem cells
34
why are stem cells developmentally restricted
to ensure progeny differentiate to the appropriate cell type
35
what do embryonic stem cells retain
nearly unrestricted developmental potential
36
what does pluripotent mean
can give rise to all cell types and tissues in an organism
37
what is an example of a pluripotent cell
embryonic stem
38
what are iPS cells
induced pluripotent stem cells
39
can you produce pluripotent stem cells without the use of embryos
yes
40
can differentiated cells be taken from an adult
yes
41
how can you produce pluripotent stem cells without embryos
- differentiated cells taken from an adult
- grown in culture
- reprogrammed into an ES-like state
42
which transcription regulators need to be modulated in expression when forming iPS cells
- Oct4
- Sox2
- Klf4
43
Differentiated cells can be taken from an adult, grown in culture, and reprogrammed into an ES-like state are called what
induced pluripotent stem cells
44
which cell types are used to form organoids
- ES (embyonic stem)
- iPS (induced pluripotent stem)
45
which cell type are often used to study and treat genetic diseases
iPS
46
what is often used to study organ development and how it can be impacted by disease
organoids
47
how are organoids formed
ES and iPS cells can be made to proliferate, differentiate, and assemble into organoids
48
cancer cells are defined by which heritable properties
- they and their progeny proliferate in defiance of normal constraints
- they invade and colonize territories normally reserved for other cells
49
when are benign tumors formed
when the cells proliferate in defiance of normal
constraints, but DONT invade and colonize territories normally reserved for other cells
50
when do tumors become cancerous
when the cells invade and colonize territories normally reserved for other cells (becomes malignant)
51
what happens when tumors become malignant
can spread, leading to secondary tumors or metastases
52
what is the underlying cause of cancer
- a genetic disease
- **somatic mutation**
53
most identified agents known to promote cancer development are what
mutagens
54
how do mutagens promote cancer development
cause changes in the sequence of DNA
55
what are passenger mutations
found in cancer but don't cause the disease
56
what are cancer-critical or driver mutations
actively promote cancer but do not act alone
57
outside of environmental factors, why are we still prone to cancer
accumulating spontaneous mutations
58
which spontaneous mutations make us prone to cancer
- passenger mutations
- cancer-critical or driver mutations
59
what 3 main things work together to cause cancer
- alterations in cell growth
- alterations in cell proliferation
- alterations in cell survival
60
why do many cancer cells speed up the aquisition of mutations
because they're genetically unstable
61
what contributes to genetic instability
- defects in DNA replication
- defects in DNA repair
- defects in cell-cycle checkpoint mechanisms
- mistakes in mitosis
- abnormal chromosome numbers
62
malfunctions in mitosis leads to what
- **chromosomal damage**
- chromosome breaks, rearrangements, aneuploidy
63
what is aneuploidy
gain or loss of whole chromosomes
64
what is given to cells with accumulating mutations that lead to cancer
competitive advantage
65
what happens as an initial population of cancer grows
- new chance mutations occur
- some are favoured by natural selection (enhance proliferation and survival)
66
what may further the development of cancer by altering selection pressures in tissues
environmental and lifestyle factors (like obesity)
67
how do environmental and lifestyle factors further favour the development of cancer
alters selection pressures in tissues
68
what are general characteristics of cancer
- can survive typically lethal stress and internal derangement
- they can proliferate indefinitely
- secrete signals that influence the behaviour of cells in surrounding tissue
- can survive and proliferate in inappropriate locations
- most are genetically unstable
- abnormally avid for nutrients
- abnormally invasive
- reduced dependence on external signals for survival, growth, division
69
what are the most dangerous mutations in many cancer-critical genes
render the encoded protein hyperactive
70
what is a common atribute of the gain-of-function mutations in cancer-critical genes
- **have a dominant effect**
- only one copy of the gene needs to be mutated to promote cancer development
71
genes susceptible to gain-of-function mutations are called what
- **proto-oncogenes**
- once they mutate, they are called oncogenes
72
once proto-oncogenes have been mutated, what are they called
oncogenes
73
what kind of gene are loss-of-function genes
- **recessive**
- require both copies of the gene to be eliminated or inactivated to contribute to cancer treatment
74
what kind of mutations are those that destroy cancer activity
loss-of-function
75
how can tumor suppressor genes be silenced
- **genetic alteration**
- **epigenetic changes** altering gene expression without changing genetic sequence
76
where does colorectal cancer most commonly occur
- older demographics
- those who are genetically predisposed to earlier development
77
the onset of colorectal cancer is foreshadowed how
by the development of many little tumors (called polyps)
78
the development of polyps is due to what
- the deletion or inactivation of a tumor suppressor gene (adenomatous polyposis coli APC)
- inherited one mutated copy and one normal cop
79
what is the class and effect of Ras gene mutation
- proto-oncogene
- activating mutations: render the Ras protein continuously active, promoting cell proliferation
80
what is the class and effect of β-catenin gene mutation
- proto-oncogene
- activating mutations: make it resistant to degredation, promoting cell proliferation
81
what is the class and effect of p53 gene mutation
- tumor suppressor gene
- inactivation: allow cancer cells to continue to survive and divide, even in the presence of damaged DNA
82
what is the class and effect of APC gene mutation
- tumor suppressor gene
- inactivation: excessive proliferation in intestinal crypt
83
what is the class and effect of Brca1 and Brca2 gene mutation
- tumor suppressor gene
- inactivation: allows cancer cells to continue to survive and divide in the presence of massively damaged DNA
84
describe the pathway of cumulative mutation needed for metastasis
85
what are some established methods of cancer treatment
- surgery
- radiation
- chemotherapy
86
what are some novel methods of cancer treatment
- targeted drug treatment
- immune activation
87
what is targeted drug treatment and how does it treat cancer
raise genetic instability in cancerous cells while normal cells persist through repair mechanisms or block activity of specific oncogene products
88
how does immune activation treat cancer
leads immune cells to protein structures unique to cancerous cells or neutralize inhibitory cell surface proteins to prevent inactivation of immune cells
89
what are the 2 major classes of genes critical for cancer
- oncogenes
- tumor suppressors
90
