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SCRA > 5. stem cell niches > Flashcards

5. stem cell niches Flashcards

1
Q

what are the three difference fates of a stem cell?

A
  • self-renew
  • differentiate
  • remain quiescent
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2
Q

what helps to regulate a stem cells function?

A

the stem cell niche

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3
Q

why is it important for a stem cell to have a niche?

A

the niche incorporates lots of signals so that the stem cell knows what it needs to be going
e.g. if there is an injury, the stem cell will know to adjust its progeny production accordingly

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4
Q

what is the stem cell niche?

A

a microenvironment where stem cells reside and receive stimuli to determine their fate

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5
Q

name one role of the stem cell niche?

A

to keep stem cells protected

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6
Q

what is an example of something that contributes to the niche but is not localised within the stem cell microenvironment?

A

hormones can regulate stem cell function but may be produced far away from the microenvironment

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7
Q

what is the difference between the stem cell microenvironment and the niche?

A
  • the microenvironment is small physical location where the stem cell resides e.g. neighbouring cells and ECM
  • the niche is everything that regulates the stem cells function e.g. hormones and blood
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8
Q

what occurs when adult stem cells are removed from their niche?

A

they differentiate

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9
Q

what did Schofeild hypothesise in 1978?

A
  • stem cells remain stem cells due to their locations and thus interactions made with other cells.
  • when they produce progeny, unless they can occupy a similar stem cell niche they will proliferate and differentiate
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10
Q

what is seen when HSC from BM are transplanted into mice? and what did this show?

A
  • white patches of progenitors on the spleen.
  • the number of patches corresponds to the number of HSC injected.
  • these could not reconstitute an irradiated mouse’s BM
  • this showed that there as something in the BM which allowed the HSC to remain HSC
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11
Q

can the niche exist in the absence of the stem cell?

A

yes - it is an area that can host the stem cell

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12
Q

what two contacts are essential in the niche?

A

cell to cell and cell to matrix contacts

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13
Q

vasculature is often presents in niches - what sort of signals to these provide?

A

humoral signalling

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14
Q

describe the gonads of C. elegans

A
  • gonad germ stem cells are in contact with distal tip cells
  • when they lose contact with this they start to proliferate and differentiate into germ cells
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15
Q

describe drosophila testes

A
  • somatic stem cells and germ stem cells both in contact with hub cells
  • as they lose contact with hub cells they proliferate and differentiate
  • somatic stem cells become somatic cyst cells
  • germ stem cells become spermatogonia
  • somatic cyst cells are vital for spermatogonia function and so both cells remain in contact throughout differentiation
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16
Q

give an example of a system where the differentiation of two lineages occurs side by side?

A

in drosophila testes, the differentiation of somatic stem cells and germ stem cells occurs side by side

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17
Q

where is the germ stem cell niche in Drosophila ovaries?

A

the germarium

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18
Q

describe drosophila ovaries

A
  • terminal filament and cap cells make contact with anterior of germ stem cells
  • as contact with these cells is lost cells begin to differentiate into cytoblasts
  • cytoblasts continue to divide until they are surrounded by somatic follicle cells
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19
Q

what is Dpp?

A

Dpp is a highly localised niche signal that maintains germ stem cells by supressing Bam transcription (which is essential for GSC differentiation)

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20
Q

when Dpp signalling is manipulated and reduced what will occur?

A

germ stem cells will differentiate

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21
Q

describe the skeletal muscle niche

A
  • stem cells are localised at the edge of muscle fibres
  • they also make contact with the basal lamina
  • the progeny of the stem cell become part of the niche (muscle fibres)
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22
Q

what will happen to muscle stem cells in vitro by themselves? and the addition of what will stop them from doing this?

A
  • muscle stem cells alone in vitro will differentiate

- the addition of muscle fibres will stop the differentiation and allow them to remain as stem cells

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23
Q

where does hematopoietic stress shift the HSC niche to?

A

extramedullary sites outside the bone marrow

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24
Q

perturbing and changing levels of something in the niche may have an affect or may not, why is this?

A

cells can contribute to the niche in a unique or redundant manner

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25
Q

heterogeneity in HSC raised what idea?

A

distinct niches home different sub-populations of HSC

26
Q

determining what cells neighbour HSC in BM has been hard, why is this?

A
  • it is hard to maintain integrity of BM during sectioning

- complexity of immunostaining method necessary to identify HSC

27
Q

isolation of HSC by flow cytometry is easy. why is identification of HSC within the tissue much harder?

A
  • immunoflourescent markers used by flow cytometry are two complex for microscopy
  • less reliable marker with more specificity must therefore be used (BrdU/H2BGFP LRC)
28
Q

why is using label retention as a marker of HSC not very good?

A

vast majority for BM cells that retain their label are not HSC

29
Q

what can be used in combination of label retention to identify HSC?

A

positive and negative staining for CD (cluster of differentiation) proteins

30
Q

give an example of three factors that contribute to the HSC niche?

A

blood vessels, osteoblasts and mesenchymal stromal cells

31
Q

what three factors ensure HSC are localised to the niche?

A
  • SDF1 produced by osteoblasts binds chemokine receptor on HSC
  • calcium released by osteoclasts binds G coupled protein receptor of HSC
  • VCAM expressed on surface of endothelial cells and osteoblast alpha-4-beta-1-intergrin on HSC
32
Q

interactions with what cell type maintain HSC quiescence?

A

osteoblasts

33
Q

what will the over expression of Dkk1 by osteoblast lead to?

A

HSC self-renewal impairment

34
Q

describe the process by which HSC can be found in peripheral blood

A
  • HSC are trafficked in and out of the bone marrow

- they stay in the blood for about 3 minutes

35
Q

what does the short time that HSC are found in the blood suggest?

A

that they are maintained as HSC in the BM

36
Q

what regulates the different number of HSC found in the blood at morning and evening?

A

circadian rhythm

37
Q

what happens to HSC injected into blood?

A

they will home to the BM

38
Q

what do HSC use to extravasate from the BM?

A
  • they roll along the endothelium
  • adhere to the endothelium, mediated by VCAM and selectins
  • migrate through the endothelium
39
Q

the mechanism that HSC use to extravasate the BM is a similar mechanism employed by what other cell type?

A

lymphocytes

40
Q

what mediates homing of HSC back to the BM?

A
  • SDF1 produced by osteoblasts and bone marrow stroma cells is a chemokine which is produced in high levels in the BM
  • SDF1 binds to HSC chemokine receptor CXCR4
41
Q

what treatment can cause HSC mobilisation into the blood?

A

G-CSF treatment

42
Q

how does G-CSF work?

A

G-CSF binds receptors on monocytes

when this occurs, monocytes supress osteoblasts and so reduce localisation signals to HSC

43
Q

the sympathetic nervous system has what affect of HSC niche?

A

it has been shown to regulate the attraction of HSC to their niche

44
Q

in combination with G-CSF, what has been shown in increase HSC mobilisation?

A

b2 adrenergic agonists i.e. something that stimulate adrenergic neurons

45
Q

how does stimulating adrenergic neurons increase HSC mobilisation?

A

they release norepinephrine which supresses osteoblasts

46
Q

it is possible that G-CSF may also act directly on adrenergic neurons?

A

yes

  • this stimulates the production of norepinephrine
  • neurotransmitters may also potentially regulate HSC mobilisation
47
Q

why is G-CSF given after chemotherapy?

A
  • chemotherapy reduces bodies ability to make white blood cells and so makes patient more susceptible to infection.
  • G-CSF strengthens the immune system by mobilising HSC
48
Q

give an example of how the progeny of HSC are part of the niche?

A

regulatory T cell, macrophages and megakaryocytes are in the vicinity of HSC and have been shown to effect their localisation and function

49
Q

what is the difference between the inter-follicular epidermis of mouse and humans

A

humans have a thicker inter-follicular epidermis as we don’t have hair as an additional protective barrier

50
Q

what is anagen?

A

the growing phase of the hair follicle

here the dermal papilla is at maximal size

51
Q

what is the resting phase of a hair follicle called?

A

telogen

the hair follicle is smallest at this point

52
Q

what is the hair follicle bulge and what is it composed of?

A

the bulge is the stem cell niche that is composed of dermal cells

53
Q

what does the dermal sheath do?

A

the dermal sheath surrounds the hair follicle

and contains progenitor cells which are recruited during anagen

54
Q

what is the function of the dermal papilla?

A

it regulates hair follicle development and growth

55
Q

where is the reservoir of multipotent stem cells in the hair follicle located?

A

the dermal papilla

56
Q

which glands release their content into the hair follicle?

A

apocrine gland

57
Q

when stem cells in the hair follicle proliferate where do they move?

A
  • they move downwards towards the bottom of the hair follicle of the growing hair
  • as they differentiate they move upwards out the follicle
58
Q

what are the three phases that the postnatal follicle undergo?

A

catagen, telogen and anogen

59
Q

what happens in catagen?

A

this is the regression phase where the hair follicle shinks which is mediated by apoptosis

60
Q

where are stem cells found in the intestine? and where is it located?

A

the crypt

the base of the vili

SCRA (19 decks)

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