Adult stem cells Flashcards

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1
Q

Why have adult stem cells?

A
  • Cells in the body die due to mild damage/ injury

- So there must be cells within the tissues to regenerate these cells

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2
Q

What are the characteristics of adult stem cells?

A
  • Multipotent
  • Tissue specific
  • Build and repair tissue
  • Difficult to isolate maintain in vitro
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3
Q

Where can adult stem cells also be derived from?

A

Foetal tissue

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4
Q

What must stem cells do in order to repair tissues?

A

1) Supply large numbers of differentiated cells
2) Protect themselves from accumulating mutations
3) Stop themselves from aging

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5
Q

Why is it important to limit the number of cell divisions of an adult stem cell?

A
  • Adult stem cells have much lower levels of telomerase than ES cells
  • Therefore, with each DNA replication, telomeres willl shorten until the cells age, when chromosomes begin to be eroded
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6
Q

What are telomeres?

A
  • Repetitive DNA sequence (TTAGGG)
  • Cap the ends of linear chromosome
  • Buffer, get eroded instead of genes
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7
Q

Describe the generic adult stem cell model

A

1) Quiescent stem cell undergoes one asymmetrical division into a transit stem cell when damage occurs
2) Transit stem cell enters the cell cycle and expands to produce progenitor cells
3) Progenitor cells expand to give differentiated derivatives

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8
Q

What are the advantages of the adult stem cell model?

A
  • Limits the number of divisions that the ASC has to make

- Protecting the ASC against gaining mutations and aging

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9
Q

What are the implications of the ASC model?

A
  • Cells flow through in a unidirectional manner
  • Differentiation becomes resticted
  • Ordered and irreversible fate decisions
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10
Q

Why doesn’t the generic ASC model apply to ALL adult stem cell models?

A

1) Not all adult stem cells are multipotent
2) Not all ASCs are quiescent
3) Flow through hierarchy is not always unidirectional

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11
Q

Example of ASCs which are not multipotent?

A

1) Epidermal basal cells
- Only make keratinocytes
- UNIPOTENT

2) Germ cells

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12
Q

Examples of ASCs which are not quiescent

A

1) Interstianal crypt
- Stem cells at the base continuously dividing
- Leading to transit amplifying cells

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13
Q

What does quiescent mean?

A

Have a period of inactivity/ dormancy

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14
Q

Examples of ASCs where the flow through the hierarchy is not unidirectional?

A

Trachea
- Damage can cause the loss of basal stem cells

  • The ‘differentiated’ clara cells above the basal layer can infill and DEDIFFERENTIATE into basal stem cells
  • Basal stem cells then form a clonal patch of cells, reforming the basal layer
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15
Q

What are CBC cells and what do they give rise to?

A
  • Crypt base columnar cells
  • The long term stem cells of the small intestinal crypt-villus unit, which continuously differentiate
  • Give rise to enterocytes, goblet cells, paneth cells, enteroendocrine cells
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16
Q

What is the marker of CBC cells/

A

Lgr5+

17
Q

What are +4LRC cells and what can they do?

A
  • Another stem cell population in the small intestinal crypt-villus unit
  • Can revert back to Lgr5+ stem cells
18
Q

How are the stem cells of the small intestine different to those of the blood?

A
  • No G0 stage

- Constantly proliferating

19
Q

What stem cells can mammary stem cells give rise to?

A
  • Unipotent myo-SC

- Bipotent Lum-SC

20
Q

What are the stem cells for skeletal muscle?

A

Satellite cells

21
Q

What occurs when there is damage to the muofibre?

A

Satellite cells re-enter the cell cycle and undergo either:

1) Symmetric division to remake the stem cell pool

OR

2) Asymmetric divsion to make the myofibres

22
Q

How are satellite cells different to the SC in the blood?

A
  • They are unipotent

- Only make myoblasts

23
Q

What is a ‘niche’ in ecology?

A

The role and position a species has in its environment

24
Q

What is a ‘niche’ in stem cell biology?

A

A local tissue microenvironment that hosts and influences the behaviours and characteristics of stem cells

  • As cells move away they lose the signals from the niche and are forces into differentiation
25
Q

Why are stem cells hard to grow in vitro/

A

In the body stem cells sit in niches, which are hard to mimic in vitro

26
Q

What is the basic idea of the stem cell niche?

A

1) Has a defined anatomical location
2) Regulates self-renewal
3) Removal of the niche results in cellular differentiation

27
Q

What is the occupancy concept of a niche?

A
  • Cell-cell adhesion/interaction between stem cells and niche cells
  • Locates SCs near the niche (near to the self-renewing signals)
28
Q

What is the fate concept of a niche?

A
  • Signals from the niche regulate cell self- renewal, survival and maintenance
  • May have signals which prevent differentiation genes being switched on
29
Q

What is the assymetric division concept of a niche?

A
  • The physical organization of a niche can polarize the stem cells
  • Signals from ONE side of the cell (closest to the niche)
  • Ensures asymmetirc division (generate a stem cell AND a differentiated cell)
30
Q

What does a niche provide in mammals?

A

1) Physical support
2) Soluble factors
3) Cell-mediated interaction
4) Maintenance and regulation of the functions of stem cells

31
Q

What cells do niches contain?

A
  • Stem cells

- Stromal support cells

32
Q

How do the cells within niches interact with each other?

A

1) Cell- surface junctionn
2) Gap junctions
3) Soluble factors

33
Q

What are soluble factors?

A

FGFs
BMPs
WNTs

  • Act locally and diffuse throughout the niche
  • Autocrine and paracrine
34
Q

What do the extracellular/ cell interactions allow?

A

1) Anchoring for stem cells to the niche

2) Polarity cue for stem cell mitosis
- Which plane of division
- Symmetrically (form 2 stem cells
or asymmetrically (form stem cell and daughter cell)

3) A platform for signalling
- Spatial cues
- Mechanical inputs

35
Q

Where is the stem cell location of the skeletal muscle?

A

Between the basement membrane and muscle fibres

36
Q

Where is the stem cell location of the blood?

A

In the bone marrow

37
Q

Where is the stem cell location of the intestine?

A

CBC at crypt base

38
Q

What are the niche components of the intestine?

A

Paneth cells