Cell Differentiation, cell death and stem cells Flashcards
define a totipotent stem cell
it has the potential to differentiate into all cell types in the body including placental tissue e.g. the zygote
define a pluripotent stem cell
- As cells become located in the embryo they become pluripotent these cells can differentiate into a wide number of cells in the body but not all
define a unipotent stem cell
a reserve population that can be used to regenerate new cells of one lineage, for example satellite cells repair damage to muscles and repair cells
what are stem cells
- Stem cells are biological cells that can differentiate into other types of cells and can divide to produce more of the same type of stem cells
what are the characteristics of stem cells
- Being unspecialised and undifferentiated
- The capability of dividing and renewing themselves for long periods
- The ability to give rise to any type of specialised cells as they are unspecialised
what is differentiation
- This is the process which cells undergo to transform from a less specialised cell to a more specialised cell in order to grow into their function
what are the three basic categories of cells found in the body
- Germ cells
- Somatic cells
- Stem cells
what do transcription factors do
- Transcription factors turn on at different times during cell differentiation
- TF act on gene expression and alter the cells final specification
- As cells mature and go through different stages different transcription factors can act on gene expression and change the cells specification/differentiation
- Bind to the receptor within the cytoplasm and goes into the nucleus and switches on and off genes
- Depending on what the environment is around the cell at the time of proliferation it can influence the differentiation
what do transcription factors effect
- This changes the effects of the next generation of cells and future cell lineages
what is a stem cell niche
- A stem cell niche is the specific microenvironment in which stem cells are found
- Factors in the microenvironment act on embryonic stem cells to regulate their gene expression profile and promote their differentiation
what do niche factors act upon
- Niche factors act on embryonic stem cells to alter gene expression and this is mediated by transcription factors
- This means the environment can influence what type of stem cell it changes in to
what are the two commitment stages
- specification
- determination
what is specification
- capable of differentiating into one cell type when placed in a neutral environment, but not when placed in a non-neutral environment, it is reversible
- This means that at this point a stem cell has a determined fate and if placed into the neutral environment it will follow the fate but if we move the stem cell into a different environment it will become a different differentiated cell therefore changing the cell type and reversing the differentiation that was originally intended
what does determination mean
– capable of differentiating into one cell type even when placed into another embryonic region, this is irreversible
- At this point the cell has a determined fate but if it is placed into a neutral environment it will not follow this fate, for example a predetermined mesenchymal will become an osteocyte even if placed into a different place therefore it is irreversible
why are the commitment stages important
- Tissues need to be regenerated constantly
- Especially tissues under near constant stress, the tongue or skin
- Regenerative medicine would heal after burns
what is dedifferentiation
is when a cell reverts to a less specialised progenitor state within a discrete lineage
what is trans determination
in which a cell dedifferentiates to a less-committed progenitor state and then switches lineages to re-differentiate to a cell type in a new lineage
what is transdifferentiation
in which a cell moves directly from one lineage to another without moving through a dedifferentiated or pluripotent intermediate
describe the epigenetic landscape
- Processes of cell fate decisions
- Top of the mountain is the totipotent cell
- Bottom of the mountain are differentiated cells that differentiate depending down which valley they follow
what is necrosis
– leads to release of cell content, causing an inflammatory response
what is apoptosis
carefully orchestrated by phagocytic cells to avoid the release of cell contents
what are the external factors of necrosis
- High or low temperatures
- Trauma
- Snake or spider bites
what are the internal factors of necrosis
- Immune system
- Oxidative stress
what is the treatment for necrosis
- Antioxidants
- Surgical removal of necrotic tissue
- Maggot debridement therapy – remove necrotic tissue and supress infection
what is apoptosis used for in adulthood and development
During development
- Nervous system
- Fingers and toes – separate them
- Approximately 50% more cells produced than are needed
Adult
- Between 50 and 70 billion cells die each day due to apoptosis in average adult human
apoptosis cannot be
stopped once it has started as it is highly regulated
what are the two different pathways to apoptosis
- intrinsic pathway
- extrinsic pathway
what does the intrinsic pathway target
- targets the mitochondria
what does the extrinsic pathway target
- splits into two further pathways TNF induced pathway and FAS pathway
what do both the pathways do
they work by attaching to a death receptor in order to imitate a caspases reaction
what are caspases
- a family of proteases that play a role in cell death
what are the 2 classes of apoptotic caspases
- initiator caspases
- executioner caspases
what do the initiator caspases divide into
divide into caspase 2, 8 and 9 – take the initial signal from the TNF or FAS pathway
what do the execution caspases divide into
divide into 3 6 and 7 - these cause the membrane alteration, organelle reduction, nuclear fragmentation and cytoskeletal disruption
what are the other caspases
- Other caspases are non-apoptotic – inflammation
How do stem cells differ from other cells
- They can divide to renew themselves indefinitely – self renew
- Can generate specialised cell types – multipotent or unipotent
- The environment around them controls their activations – niche
describe characteristics of apoptosis
- Programmed cell death
- Beneficial - prevent tumour formation
- No inflammatory response – avoids release of cell contents to prevent further injury
- Membrane blebbing and formation of apoptoic bodies form blebs, nuclear collapse, engulfed by white blood cells
- Affect single cells
- Occurs in development and adult
- Highly regulated as it cannot be stopped once it has started
describe the characteristics of necrosis
- Necrosis
- Premature death of cells and living tissue, abnormal
- caused by factors external to the cell or tissue such as infection, toxins or trauma
- Detrimental premature cell death
- Significant inflammatory response, leads to release of contents, can result in being chronic
- Cells swell rupture and release intracellular contents, cause ATP depletion, metabolic collapse, cell swelling and rupture leading to inflammation
- Affects group of neighbouring cells
Due to external factors
what are the two methods of stem cell division
- asymmetrically
- ## symmetrically
describe asymmetrical divison
- If it is an asymmetrical division one daughter remains a stem cell and the other becomes a terminally differentiated cell
what are the two types of symmetrical cell division
symmetric differentiation
symmetric self renewal
describe symmetric differentiation
is when the stem cell divides into two differentiated cells
describe symmetric self-renewal
stem cell divides into two identical stem cells – stem cell expansion
what can stem cells be used for
- regenerative medicine such as skin grafts
how do you make stem cells
- Patients somatic cells reprogrammed using conditions/factors that induce self-renewal and pluripotency to produce patient specific iPS cells
- iPS induced to form ectodermal epithelial cells and neural crest in vitro
- combine these so they interact to produce a tooth
what is senescene
- irreversible proliferative (cell cycle) arrest
what is senescence caused by
factors that stress the cell such as radiation
describe the function of senescene
- acts as a self defence mechanism which prevents proliferation of damaged cells
why might cells go into senescence and not apoptosis
- same stimulus that causes apoptosis
- might not go into apoptosis because cell is there to maintain the tissue structure, we don’t know why one occurs over the other yet
what mutations can cause cancer in stem cells
mutations in
- specific stem cells
- stem cell progenitors
- form differentiated cells
cancer can…
can reappear, go back into the cell cycle and form the cancer again and has tumour progression
what does self renewing do in cancer
- self-renew by dividing and give rise to many cell types that constitute the tumour and therefore form tumours
what causes cancer
- occurs due to loss of apoptosis or senescence
why do premalignant tumours have restricted growth
- premalignant tumours will contain a mixture of cells
- cells undergoing apoptosis/senescence will outweigh the number of cells undergoing proliferation
why down malignant tumours have restricted growth
malignant tumours will have higher numbers of proliferating cells than cells undergoing apoptosis or senescence, this explains the wide spread growth
what is the number of cells in a multi organism regulated by
- controlling rate of cell division
- controlling rate of cell death
describe difference in telomeres in adults and elderly
- in young or adults stem cell pool filled fully and cells enter cell cycle easily – regenerate tissues easily
- in the elderly stem cell telomeres shorter and the stem cell pool is reduced – tissue regeneration reduced is slow
what happens if stem cells express a high level of telomerase
due to a mutation or an epigenetic change activates telomeres expression, they will proliferate faster and more efficiently this increases the probability of tumour forming
what does telomerase do
it enables the lengthening of telomeres
what happens with a low level of telomerase activity
- the level of telomerase activity is low or absent in the majority of stem cells regardless of the proliferative capacity, with ageing stem cells are unable to continue to replenish the tissues of an organism with functional differentiated cells and therefore tissue regeneration is reduced
what happens to a telomere with each cell division
DNA is lost with each cell division, when telomere length reaches a critical limit the cell undergoes apoptosis or senescence
what is the stem cell length maintained by in embryonic stem cels
- in embryonic stem cells telomere length is maintained by the enzyme telomerase – adds telomeric repeats onto the chromosome ends and prevents the replication dependent loss of the telomere and cellular senescence in highly proliferative cells of the germline and majority of cancers
