Lecture 3 Adult stem cells Flashcards

1
Q

What structure do cells at the periphery of the mammalian blastocyst form and from what fate is this

A

Cells on the outer periphery of a human/mammal embryo assume a different fate; the trophectoderm that forms the placenta

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2
Q

What is the name given to the cells that occupy the inside of the trophoblast

A

Inner cell mass

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3
Q

What is the significance of the cells inside the trophoblast not occupying the full space

A

The cells of the inner cell mass cluster at one side, the cells closest to the trophectoderm will give rise to the epiblast whereas the cells furthest from the trophectoderm will give rise to the hypoblast

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4
Q

From which region of the human embryo are human ES cells found

A

Inner cell mass

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5
Q

Define a stem cell

A

A cell capable of endless self-renewal and can give rise to a daughter that can give rise to several lineages

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6
Q

How is a progenitor cell different to a stem cell

A

A progenitor cell is only capable of limited self-renewal as well as limited differentiation propensities

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7
Q

Describe what is known at the 32 cell stage

A

Cells on the outside know they are different from the inner cells

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8
Q

Outer cells become ______

Inner cells become _____

A

Trophectoderm

Embryo

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9
Q

Cells which are taken from the inner cell mass and are cultured are known as

A

Embryonic stem cells

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10
Q

Two properties of stem cells

A

Endless self-renewal

Differentiation to multiple lineages and fates

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11
Q

Can specialised cells undergo mitosis?

A

NO

Except T-cells of liver cells

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12
Q

Can stem cells divide by mitosis?

A

Yes

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13
Q

What is between stem cells and specialised cells

A

Intermediate progenitor cells

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14
Q

Is the DNA in the dividing stem cells in self-renewal or differentiation the same as the original stem cell?

A

Yes

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15
Q

What do dividing stem cells in humans vs fruit flies usually form?

A

It is believed that human stem cells divide to form either 2 stem cells or 2 specialised cells. Fruit fly stem cells can divide to make one stem cell and one more specialised cell in a single division

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16
Q

Why do SCs need to self renew

A

To maintain stem cell pool

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17
Q

Why do SCs need to differentiate

A

In order to replace dead or damaged cells through life

OR add new cells to increase size or generate cells needed at a specific time point

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18
Q

Describe the location of

Embryonic SCs
Adult SCs

A

Inner cell mass of the blastocyst

Tissues of the body

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19
Q

Where are embryonic stem cells taken from

A

Blastocyst inner cell mass of early vertebrate mammalian embryo which hasn’t yet implanted into the womb

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20
Q

Where are embryonic stem cells taken from the equivalent of what stage in Xenopus

A

32 cell stage of a Xenopus

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21
Q

What do the embryonic stem cells usually form

A

The body of the embryo

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22
Q

Embryonic stem cell potency

A

Pluripotent

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23
Q

Why aren’t ES cells used in medicine? What are used

A

Increased likely hood of rejection since they will have a different genetic make up

iPS cells used

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24
Q

Why are ES cells not useful for regenerative medicine?

A

They would derive from non-host cell tissue

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25
Q

What are ES cells useful for?

A

To study specific population and for drug signalling

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26
Q

What can ES cells be cultured into?

A

Self-renew into stem cells
OR
Forced to differentiate into specific cell fates with certain signals.

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27
Q

How are ES cells cultured?

A
  1. ES cells taken from inner cell mass
  2. culture in lab to grow more cells - fluid with nutrients
  3. these differentiate into all types of specialised cells depending on the conditions
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28
Q

As development proceeds, what occurs to somatic cells

A

They differentiate but are not mitotic

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29
Q

Where were adult/tissue-specific stem cells first recognised? Where now? Potency?

A

Multipotent
These were first recognised in bone marrow, liver, gut and skin. They are now recognised in other tissues e.g. brain and muscle.

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30
Q

Functions of adult stem cells (3)

A
  • Maintain cell populations
  • Help with the healing process
  • Play a role in ageing
31
Q

Define undifferentiated

A

Describing a cell which has not yet acquired special structure or function pertaining to an immature or primitive cell

32
Q

Define self-renewal

A

Ability to go through numerous cycles of cell division while maintaining the undifferentiated state

33
Q

Define differentiate

A

The process by which a less specialised becomes a more specialised cell type

34
Q

Define specialised

A

Specialised cells perform more specialised functions in multicellular organism

35
Q

Describe adult stem cells

A
  • Undifferentiated (or only partially differentiated) found in tissues and organs
  • Can self-renew and differentiate to become most/all of the specialised cell types within that specific lineage
36
Q

What is homeostasis

A

Ability to regulate internal conditions, usually by a system of feedback controls. This stabilises health and functioning regarding the outside changing conditions

37
Q

What is cellular homeostasis

A

constant or periodic generation of new cells to replace other cells or the addition of cells as needed

38
Q

Give an example of cellular homeostasis

A

Pregnant females produce more red blood cells. RBCs are made continuously through life from haematopoietic stem cells in the bone marrow. Haematopoietic stem cells respond to increased levels of oestrogen found in pregnant females, to become hyper-activated and make many more daughter cells

39
Q

How can adult stem cells carry out cellular homeostasis?

A

Regeneration

Replacement

40
Q

Types of Adult Stem Cells

A
  • Hematopoietic stem cells: blood and immune system
  • Mesenchymal stem cells: bone, cartilage, fat, muscle, tendon/ligament
  • Epithelial stem cells: skin, gut, other linings
  • Muscle stem cells
  • Neural stem cells: neurons, glial cells, retinal cells
41
Q

How are adult stem cells prevented from differentiating

A

Residing in a niche - specialise microenvironment

42
Q

How do adult stem cells remain in a niche?

A

• Stem cells may be anchored by cell adhesions molecules (CAMs) or receptor ligand interactions to support stromal/support cells

43
Q

Describe signalling in the niche

A

o Rich blood supply

o Dense neuronal inputs

44
Q

In general what are niches composed of

A

• In general niches are composed of a variety of cells that secrete signals involved in proliferation versus differentiation, and blood cells

45
Q

What two lineages to HSCS give rise to

A

Myeloid

Lymphoid

46
Q

Cells of the myeloid lineage

A
o	Monocytes
o	Macrophages 
o	Neutrophils
o	Basophils
o	Eosinophils 
o	Erythrocytes 
o	Megakaryocytes/platelets 
o	Dendritic cell
47
Q

Cells of the lymphoid lineage

A
  • T-cells
  • B-cells
  • NK-cells
48
Q

Where are HSC found

A

Found in the bone marrow from very early on in development as well as in umbilical cord blood and placental tissue

49
Q

In HSC niche, what do stem cells cycle between

A

active and quiescent form

50
Q

Why do niches need endothelial capillary cells

A

• Stem cells respond to physiological signals – including blood borne factors so niches need endothelial capillary cells

51
Q

What acts on HSCs

A

Stem cell factor secreted by support cells

52
Q

Muscle stem cells are

A

Satellite cells

53
Q

Where are satellite cells found

A

Outside of the muscle fibre - under the basal lamina

54
Q

What causes self-renewal of satellite cells

A

Pax7

55
Q

What causes differentiation of satellite cells

A

MyoD

56
Q

How are stem cells maintained

A

Through asymmetric cell divisions

57
Q

What will mesenchymal stem cells dif into

A
  • Chondrocytes (cartilage cells)
  • Myocytes (muscle cells)
  • Adipocytes (fat cells)
  • Epithelial cells including osteoblasts (tendons, ligaments and CT)
58
Q

Where are mesenchymal stem cells located?

A

These cells are located throughout the body. Bone marrow, fat and cord blood are the easiest to isolate.

59
Q

Epithelial stem cells give rise to

A

Epithelial cells

60
Q

What % of our cells are epithelial

A

60%

61
Q

Where are epithelial stem cells located

A

Niches

62
Q

What are the three main brain areas where neural stem cells can be found

A

Subventricular zone
Subgranular zone
Hypothalamus

63
Q

Can neural stem cells renew and differentiate

A

YES

64
Q

What is the morphology of neural stem cells

A

Radial glial morphology

One end containing the cell body it is attached the VZ and a long basal extending process extends out.

65
Q

Describe the subventricular zone

A

Lining the lateral ventricles where they give rise to newly-born neurones that migrate to the olfactory bulb via the rostral migratory stream

66
Q

Describe the Sub granular zone

A

Part of the dentate gyrus of the hippocampus. Involved in the acquisition of new memory

67
Q

Describe the Hypothalamus

A

Lining the 3rd ventricle where they contribute new neurones to energy/feeding circuits
Composed largely of a large series of interconnected nuclei which act to control body homeostasis

68
Q

What physiological processes does the hypothalamus control?

A

They regulate an array of physiological processes e.g. body fluid homeostasis, thermoregulation, stress responses, energy balance, circadian rhythms, reproductive behaviours

69
Q

Where do adult stem cells and progenitor cells reside

A

Throughout the body in the stem cell niche

70
Q

Describe the stem cell niche

A

It is a particular microenvironment that fosters the growth of resident stem cells

71
Q

What activates a stem cell in a niche

A

Signals they receive and changes in their microenvironment

72
Q

Is there an ability for endless self-renewal of tissue specific stem cells?

A

It is unclear but all cells can only undergo a limited number of divisions. As you age, the stem cell pool is depleted leading to the ageing process

73
Q

Adult stem cells normally remain … for relatively long periods of time until …

A

quiescent (non-dividing)

they are activated by signals to maintain tissues

74
Q

When stem cells are activated they are…

A

Primed to divide

This may be through symmetric division to expand the stem cell pool or through asymmetric cell division to maintain the pool and give a differentiating daughter