Cell Differentiation, cell death and stem cells Flashcards

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1
Q

define a totipotent stem cell

A

it has the potential to differentiate into all cell types in the body including placental tissue e.g. the zygote

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2
Q

define a pluripotent stem cell

A
  • 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
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3
Q

define a unipotent stem cell

A

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

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4
Q

what are stem cells

A
  • 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
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5
Q

what are the characteristics of stem cells

A
  • 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
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6
Q

what is differentiation

A
  • 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
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7
Q

what are the three basic categories of cells found in the body

A
  • Germ cells
  • Somatic cells
  • Stem cells
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8
Q

what do transcription factors do

A
  • 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
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9
Q

what do transcription factors effect

A
  • This changes the effects of the next generation of cells and future cell lineages
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10
Q

what is a stem cell niche

A
  • 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
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11
Q

what do niche factors act upon

A
  • 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
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12
Q

what are the two commitment stages

A
  • specification

- determination

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13
Q

what is specification

A
  • 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
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14
Q

what does determination mean

A

– 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

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15
Q

why are the commitment stages important

A
  • Tissues need to be regenerated constantly
  • Especially tissues under near constant stress, the tongue or skin
  • Regenerative medicine would heal after burns
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16
Q

what is dedifferentiation

A

is when a cell reverts to a less specialised progenitor state within a discrete lineage

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17
Q

what is trans determination

A

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

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18
Q

what is transdifferentiation

A

in which a cell moves directly from one lineage to another without moving through a dedifferentiated or pluripotent intermediate

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19
Q

describe the epigenetic landscape

A
  • 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
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20
Q

what is necrosis

A

– leads to release of cell content, causing an inflammatory response

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21
Q

what is apoptosis

A

carefully orchestrated by phagocytic cells to avoid the release of cell contents

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22
Q

what are the external factors of necrosis

A
  • High or low temperatures
  • Trauma
  • Snake or spider bites
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23
Q

what are the internal factors of necrosis

A
  • Immune system

- Oxidative stress

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24
Q

what is the treatment for necrosis

A
  • Antioxidants
  • Surgical removal of necrotic tissue
  • Maggot debridement therapy – remove necrotic tissue and supress infection
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25
Q

what is apoptosis used for in adulthood and development

A

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

26
Q

apoptosis cannot be

A

stopped once it has started as it is highly regulated

27
Q

what are the two different pathways to apoptosis

A
  • intrinsic pathway

- extrinsic pathway

28
Q

what does the intrinsic pathway target

A
  • targets the mitochondria
29
Q

what does the extrinsic pathway target

A
  • splits into two further pathways TNF induced pathway and FAS pathway
30
Q

what do both the pathways do

A

they work by attaching to a death receptor in order to imitate a caspases reaction

31
Q

what are caspases

A
  • a family of proteases that play a role in cell death
32
Q

what are the 2 classes of apoptotic caspases

A
  • initiator caspases

- executioner caspases

33
Q

what do the initiator caspases divide into

A

divide into caspase 2, 8 and 9 – take the initial signal from the TNF or FAS pathway

34
Q

what do the execution caspases divide into

A

divide into 3 6 and 7 - these cause the membrane alteration, organelle reduction, nuclear fragmentation and cytoskeletal disruption

35
Q

what are the other caspases

A
  • Other caspases are non-apoptotic – inflammation
36
Q

How do stem cells differ from other cells

A
  • 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
37
Q

describe characteristics of apoptosis

A
  • 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
38
Q

describe the characteristics of necrosis

A
  • 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
39
Q

what are the two methods of stem cell division

A
  • asymmetrically
  • ## symmetrically
40
Q

describe asymmetrical divison

A
  • If it is an asymmetrical division one daughter remains a stem cell and the other becomes a terminally differentiated cell
41
Q

what are the two types of symmetrical cell division

A

symmetric differentiation

symmetric self renewal

42
Q

describe symmetric differentiation

A

is when the stem cell divides into two differentiated cells

43
Q

describe symmetric self-renewal

A

stem cell divides into two identical stem cells – stem cell expansion

44
Q

what can stem cells be used for

A
  • regenerative medicine such as skin grafts
45
Q

how do you make stem cells

A
  • 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
46
Q

what is senescene

A
  • irreversible proliferative (cell cycle) arrest
47
Q

what is senescence caused by

A

factors that stress the cell such as radiation

48
Q

describe the function of senescene

A
  • acts as a self defence mechanism which prevents proliferation of damaged cells
49
Q

why might cells go into senescence and not apoptosis

A
  • 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
50
Q

what mutations can cause cancer in stem cells

A

mutations in

  • specific stem cells
  • stem cell progenitors
  • form differentiated cells
51
Q

cancer can…

A

can reappear, go back into the cell cycle and form the cancer again and has tumour progression

52
Q

what does self renewing do in cancer

A
  • self-renew by dividing and give rise to many cell types that constitute the tumour and therefore form tumours
53
Q

what causes cancer

A
  • occurs due to loss of apoptosis or senescence
54
Q

why do premalignant tumours have restricted growth

A
  • premalignant tumours will contain a mixture of cells

- cells undergoing apoptosis/senescence will outweigh the number of cells undergoing proliferation

55
Q

why down malignant tumours have restricted growth

A

malignant tumours will have higher numbers of proliferating cells than cells undergoing apoptosis or senescence, this explains the wide spread growth

56
Q

what is the number of cells in a multi organism regulated by

A
  • controlling rate of cell division

- controlling rate of cell death

57
Q

describe difference in telomeres in adults and elderly

A
  • 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
58
Q

what happens if stem cells express a high level of telomerase

A

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

59
Q

what does telomerase do

A

it enables the lengthening of telomeres

60
Q

what happens with a low level of telomerase activity

A
  • 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
61
Q

what happens to a telomere with each cell division

A

DNA is lost with each cell division, when telomere length reaches a critical limit the cell undergoes apoptosis or senescence

62
Q

what is the stem cell length maintained by in embryonic stem cels

A
  • 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