Quiz 4 Flashcards
Embryonic Development Involves:
- Cell Proliferation
- Cell Differentiation
- Pattern formation and Morphogenesis
Cell Cycle
The sequence of stages through which a cell passes between one cell division and the next.
Cell cycle checkpoints Definition
Surveillance mechanisms that monitor the order, integrity, and fidelity of the major events of the cell cycle.
What are the Cell Cycle Checkpoints?
- G1/R checkpoint
- S-phase checkpoint
- G2 checkpoint
- Metaphase (M) checkpoint
G1/R checkpoint
Monitors external & internal conditions (DNA damage)
S, G2, & M checkpoints
Monitors internal conditions
During G1, cells are responsive to:
- nutrient levels
- anchorage dependance
- Mitogenic growth factors
- Anti-mitogenic TGF-beta signals
What are the choices prior to/ at R point?
- Remain in active proliferation.
- Exit from cell cycle (G0 or post-mitotic phase)
or - Apoptosis
What happens after passing the R point?
Cells commit to completing the cell cycle relatively independent of extracellular signals
What does evidence implicate about the deregulation of the G1/ R checkpoint?
the deregulation of the G1/r checkpoint is found in most if not all types of cancer cells
What happens before/during the G0 phase?
*Cells monitor internal and external conditions (signals) and make decisions about whether to continue proliferation or enter G0.
*Cells may may enter the G0 phase prior to the R checkpoint (G1 checkpoint) for a variety of reasons.
What are the three G0 states?
- Quiescent (resting, inactive)
- Senescent (not really resting or active)
- Differentiated (not active) — Terminally differentiated cells like nerve and muscle cells.
What G0 state is reversible?
Quiescent
Genes that regulate the cell cycle:
- are often mutated in cancer in two types of genes
What is the cell cycle clock?
A way to explain the molecular actions of many oncogenes and their effects on the clock ??
Proto-oncogenes
- Stimulates cell cycle progression
- Mutation in Cancer –> Gain of function mutation
-“Brake genes”
Tumor Suppressors
- Inhibits cell cycle progression
- Mutation in cancer –>Loss of function
- “Gas pedal genes”
How is genome integrity maintained?
Tumor suppressor p53 is activated in response to DNA damage
What is the p53 pathway responsible for?
- Halting the cell cycle until damage is repaired
- Initiating apoptosis
See Classic model of p53 activation
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See the Classic model of p53 activation
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p53’s function is sequestered by what?
MDM2
What are the sequential activation steps?
- Stress-induced stabilization of P53 mediated by phosphorylation
- DNA binding
- Recruitment of the general transcriptional machinery
Cell cycle molecular circuitry
Complexes of CYCLIN-DEPENDENT KINASES and CYCLINS regulate passage through checkpoints
-See figure-
How is progression through different checkpoints controlled?
Different cyclins rise and fall at different times during the cell cycle
What happens when a cyclin level reaches it’s threshold?
it binds to it’s cognate CDK
What are cyclins and CDKs regulated by?
Many different signals through signal transduction pathways
D1
Cyclin D1
Cyclin D1
Can be repressed to prevent cyclin CDK
What has been shown to possess a powerful anti-cancer effect?
Turmeric (Curcumin)
What two steps in embryonic development relate to stem cells?
- Cell Proliferation
- Cell differentiation
What are the two defining properties of stem cells?
- The ability to self-renew (self-regenerate, proliferate)
- The ability to differentiate into specialized stem cells
Differentiation
When an unspecialized early embryonic cell acquires the features of a specialized cell such as a heart, liver, or muscle cell
See the figure on cell differentiation steps
Draw Figure
Cell Potency
A cell’s ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater it’s potrncy
See the figure on the Hierarchy of Stem Cells
Draw Figure
Totipotent
- the state of a cell that is capable of giving rise to all types of cells found in an organism
- supports extra-embryonic structures of the placenta
- a single totipotent cell could reproduce the whole organism in utero
–Fertilized oocyte through 8 or 16- cell stage
Pluripotent
The state of a single cell that is capable of differentiating into all tissues of an organism, but not capable of sustaining full organism development
What is an example of Pluripotent?
Inner Cell Mass
Embryonic Stem Cell (ESC)
Primitive (undifferentiated cells derived from preimplantation-stage embryos) can divide without differentiating for a prolonged period in culture.
Known to develop into cells and tissues of the three primary germ layers
Multipotent
The ability to develop into more than one cell type of the body
Example of multipotent
Hematopoietic stem cells
What is an example of oligopotent and Unipotent?
Spermatogonial stem cells
Progenitor Cells
Divide a limited number of times and have the tendency to differentiate into specific cell types, usually unipotent, will differentiate into its “target” cell.
Which cell types have unlimited proliferation?
Zygotes
Embryonic stem cells
Multipotent stem cells
(see figure)
Which cells have limited proliferation?
Neuronal progenitor
Differentiating neuronal precursors
(see figure)
Which cells have no proliferation?
Differentiated cells
What happens as cells become more differentiated?
There is a loss of developmental potential. (POTENCY)
What do multipotent stem cells become?
Progenitor Cells
What is the typical course of embryogenesis?
It involves the specialization of stem cells into progenitor and precursor cells and then finally into adult tissue through differentiation or specialization.
Adult Stem Cells are also known as…
Somatic stem cells
Somatic stem cells
Their progeny replaces cells that are lost owing to tissue turnover or injury, thus ensuring the maintenance of tissue.
They are usually maintained in a quiescent state,and when activated, they proliferate to replenish damaged tissue
Cellular Plasticity
Describes the ability of some cells to take on the characteristics of other cells
Stem Cell Plasticity
- The ability of adult tissue-specific stem cells to switch to new identities.
- Stem Cell phenotypic potential (as opposed to normal cell fate)