Cell growth and differentiation Flashcards
What are the basic mechanisms responsible for turning a zygote into a mature multicellular organism?
Cell growth and differentiation.
Cell growth precedes differentiation, but with some overlap
Cells divide, lose potency. Cells become more specialised and eventually exit cell cycle and cell differentiation begins
What are the three groups of diseases related to cell growth and differentiation?
Developmental conditions, can be related to defects in cell growth or differentiation e.g spina bifida
Neoplasia (and metaplasia)e.g cancer, tumours
Others e.g cardiac hypertrophy
What are the two main forms of cell growth?
And what is cell growth balanced by?
Hypertrophy (bigger cells)
Hyperplasia (more cells) - most common form of cell growth in humans
Cell growth is balanced by cell death - apoptosis and necrosis
What is hypertrophy?
Cells growing bigger. Caused by cells making more macromolecules, more proteins, more membrane.
Elevated protein synthesis is driver of increased cell size e.g heart.
What is hyperplasia?
More cells, caused by cell division or proliferation - the cell cycle
What is common between cell growth and differentiation?
The mechanisms governing them.
Cell growth and differentiation are governed by integration of multiple signals
Intra (e.g checks on health and physiology of cell, energy levels, sufficient nutrients for differentiation) and extravascular signals (checks on cellular physiology, growth and inhibitory factors, cell adhesion (on outside of cell) etc.)
Promoters act as “co-incidence detectors” - when there’s the right combo of signals being received by promoter, it makes binary decision
Decision to express genes YES/NO? Governs how much is made
What do promoters do with signals?
Signals are integrated and converge on the promoters of key genes.
Promoters act as “co-incidence detectors” - when there’s the right combo of signals being received by promoter, it makes binary decision
Decision to express genes YES/NO? Governs how much is made
What do extracellular signals follow?
What are the three broad classes
Ligand receptor binding - followed by intracellular cascade.
Paracrine: produced locally to stimulate proliferation of a different cell type that has the appropriate cell surface receptor
Autocrine: produced by a cell that also expresses the appropriate cell surface receptor
Endocrine: like conventional hormones, released systemically for distant effects
What do the proteins that act as extracellular signals in cell growth and differentiation do?
Stimulate proliferation and survival – referred to as mitogens E.g growth factors and interleukins EGF, FGF, NGF, PDGF, IGF1, IL2, IL4
Induce differentiation and inhibit proliferation e.g TGFB
Can do either, promote cell growth or inhibit cell growth e.g Wnt ligands
Other signals act to induce apoptosis e.g TNFa and other members of TNF family, bind to receptor and elicit cascades causing death
What is the m phase of the cell cycle?
Mitosis. Cell divides into 2 daughter cells.
Cell leaves mitosis and enters interphases. Grows in size throughout interphase as macromolecules are synthesised.
What is the s phase?
Synthesis. Genome is copied.
What is G1 and G2?
Gap phases.
G1 is between M phase and S phase.
G2 is between S phase going back to M phase.
What cells are in G0?
How long are cells in G0?
Cells that have left the cell cycle are quiescent cells and are in G0.
In G0 indefinitely, metabolism takes over. Or can rejoin cell cycle as some stimulus makes them proliferate again.
Or they begin to differentiate., change shape and adopt a new function. Ultimately terminally differentiated and considered post mitotic cells.
How can you tell if cells are in mitosis and are G0 and G1 cells or if they are G2 cells/going into mitosis?
Measure amount of cells in cell cycle.
Cells that have just been through mitosis and are G0 and G1 cells will have diploid genome.
Cells in G2/going into mitosis will have tetraploid genome 4N. As in DNA replication after mitosis chromosomes double.
Cells in synthesis will be somewhere in between as they’re in process of replicating.
What does the FAC machine measure?
Measures the DNA content of every cell in a population by measuring the strength of the staining.
What does the area between two peaks on a FAC analysis correspond to?
image is trace for population of cells with low rate of division
Cells in S phase, between 2 and 4 copies of chromosomes.
How does the typical trace differ in a population of cells with a high rate of division?
Proportion of cells in G1/G0 have decreased, from 60% to 40%
Population in S phase has increased
G2/M doesn’t change much because it is time limited part of cell cycle
What are the three checkpoints in the cell cycle?
Restriction point. Dependent on factors e.g checks for DNA damage, if cell size big enough to be divided into two. Checks metabolite/nutrient stores are enough to get through process of synthesis and mitosis.
Second checkpoint, G2 M phase checkpoint. When cell commits to enter mitosis. Another check for DNA damage and that replication is complete, when cells divides it can guarantee there is enough chromosomal DNA for the two daughter cells
Final check point in mitosis, distinct doesn’t involve checks in DNA. Checks physical positioning of chromosomes on mitotic spindle, ensures when it separates the chromosomes are pulled apart. Ensures right number of chromosomes goes to each cell.
What triggers cell cycle arrest or apoptosis?
DNA damage, cell cycle stops, driven by expression of cyclin dependent kinase inhibtors e.g CHEK2.
Cell attempts to repair DNA using repair mechanisms - nucleotide or base exicision enzymes, mismatch repair etc
if repaired cell re-enters cell cycle, if not there is apoptosis
What happens if TP53 accumulates?
- Drives expression of CDKI, causing cell cycle arrest
- Activation of DNA repair, DNA can be repaired and can return back to cell cycle. However, sometimes damage is too bad and TP53 will activate cell death.
