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Intercal - Adaption in physiology > Satellite Cells 1 > Flashcards

Satellite Cells 1 Flashcards

1
Q

Why are stem cells(skeletal cells) important for skeletal muscle

A

skeletal cells are the stem cells of the skeletal cells cells
Genetically and metabolically very active and have a high degree of plasticity -
Hypertrophy
Hyperplasia
Fibre type switch (contraction type)
Metabolic adaptation
High regenerative capacity

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2
Q

What makes the skeletal muscle cell cycle different to other cell cycles

A

Mitotically inactive but have many nuclei

Meaning they can’t divide anymore

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3
Q

What is myogenesis

A

The formation of skeletal muscle tissue

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4
Q

What is the main stages of myogenesis

A

Mesodermal stem cells –> determined myoblasts –> terminal differentiation occurs (with growth factors) –> differentiated multinucleated myotubes

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5
Q

What is the process of embryonic myogenesis

A

Myotome derived myoblasts migrate into the limb buds

Proliferation and initiation of the myogenic program starts the formation of limb and skeletal muscle development

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6
Q

What controls the myogenic process

A

myogenic regulatory factors- they are a family of proteins

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7
Q

What are the two myogenic regulatory factors (MRF) seen at the early stages of development from mesodermal stem cells into determined myoblasts

A

MyoD
Myf 5

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8
Q

What are the myogenic regulatory factors (MRF) seen at fusion

A

Myogenin

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9
Q

What are the myogenic regulatory factors (MRF) seen during terminal differentiation (determined myoblasts to differentiated myotubes)

A

Myogenin
MyoD
MyF5
MRF4 (expressed in myofibril)

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10
Q

What is the role of the MRF family

A

They are BHLH proteins (helix-loop-helix) that bind to DNA sequences (E box) in muscle promoters

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11
Q

What regulates MRFs

A

They autoregulate

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12
Q

What are E-boxes

A

Specific DNA sequence -

CANNTG

N - can be any base

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13
Q

Why are bHLH proteins important

A

Needed for dimerisation (2 smaller similar molecules combining to form a dimer)
Needed for DNA binding

Therefore the The bHLH domain is essential for activation of myogenesis.

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14
Q

What can bHLH proteins formed dimers with

A

Myogenic bHLH can form dimers with other myogenic bHLH factors or with bHLH factors of the E12 or E47 family

E12 and E47 increase myogenesis

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15
Q

Dimerisation with bHLH and what causes inhibition of DNA binding

A

Factor Id

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16
Q

How can bHLH factors be inhibited

A

Phosphorylation inactivates myogenic transcription factors by inhibition of DNA binding

Phosphorylation is activated by growth factor signals which activate protein kinase C to cause phosphorylation

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17
Q

How does factor Id disrupt bHLH activity

A

Id disrupts dimerisation and DNA binding of myogenic bHLH proteins by ‘blocking’ E12 and E47 from binding. By blocking these from binding this results in no myogenic regulatory genes being transcribed.
Id is expressed on a high level in response to growth factors

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18
Q

How do bHLH proteins cause myogenesis

A

E12/E47 is activated by inhibition of growth factors which allows it to bind with myo (Myogenic regulatory gene promoters).

Myo and E12/E47 then binds downstream to genes of terminal differentation

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19
Q

What is MEF2 and its role

A

A myogenic transcription factor - During development and differentiation MEF2 transcription factors amplify and maintain the expression of other myogenic transcription factors. Essentially regulates myogenesis

20
Q

How is terminal differentiation (determined myoblasts to differentiated myotubes) started

A

Removing growth factors

21
Q

What has been found out on MRFs knock-out studies of mice regarding their ability to compensate

A

MyoD -/- = normal muscle
Myf5 -/- = muscle delayed but normal

Both knocked out - no muscle present

Shows level of compensation between both MRFs

22
Q

Define commitment

A

move cell to new location, still maintains its original fate

23
Q

Define determination

A

in context of muscle, expression of Myf 5/MyoD

Means the cell becomes a specific muscle cell - e/g actin

24
Q

What are satellite cells

A

Mononucleated cells which rest between the muscle fibre and basal lamina

25
Q

How are satellite cells formed

A

Determined myoblasts that have just undergone determination from mesodermal stem cells are put into a quiescent (rest) stage by MyoD and myf5 to form a satellite cell

They are formed during embryogenesis but are activated and divide at various points in life.

26
Q

What is the role of satellite cells

A

Used for muscle fibre repair and reconstruction by differentiating and proliferating when growth factors are removed.

They are very dominate, but as soon as become activated

27
Q

What activates increased satellite cells

A

Removal of growth factors

28
Q

How do satellite cells go into the quiescent stage

A

Pax7 (paired box gene 7) is crucial for satellite cell formation

29
Q

How do we know pax7 is crucial for satellite cell formation

A

Pax7 -/- transgenic animals die soon after birth due to missing satellite cells

30
Q

What is the role of Pax7

A

Paired box gene Transctiption factors are important for embryonic development

Pax7 is also essential for post-natal muscle development and maintenance

31
Q

What did Mansouri et al 1996 show about pax7 -/- mice

A

50% smaller and died within 2 weeks

Had thinner diaphragm development

32
Q

What three genes activate a quiescent satellite cell

A

CD34
Pax7
Myf5 - shows that it is destined to become a muscle cell

33
Q

What genes are important when satellite cells become a myoblast

A

Myf5
MyoD
(Pax7 becomes less important)

This makes them harder to study as more difficult to track with the constant change of markers

34
Q

What gene is important for the maturation of a myofibre/fusion

A

Myogenin

35
Q

How do satellite cells become activated and differentiated with regard to growth factors

A

Downregulate growth factor receptors when growth factor decreases and then differentiate from there.

36
Q

What happens in satillete cell quiensence

A

Dormant, small cytoplasm resulting in very little metabolism occurring.

37
Q

What has been shown about the link between satellite cells and myofibre nuclei and its link to age-related muscular atrophy

EXTRA READING - Brack 2005

A

Using myoD-knockout mice, it was found that a satellite cell defect causes inadequate nuclear replacement within myofibres. This triggers cytoplasmic atrophy in the muscle fibres because of an increase in area covered per nuclei.

It may partially explain muscle atrophy during ageing.

38
Q

When were satellite cells discovered

A

1961 by mauro looking at frog myofibres.

39
Q

What is believed to inhibit satellite cells, causing them to become quiscent.

WIDER READING - McCroskery 2003

A

Myostatin - up-regulate a cyclin-dependent kinase inhibitor called p21 and thereby inhibit the differentiation of satellite cells

40
Q

How has light exercise been shown to counteract muscle atrophy

EXTRA READING - KADI 2005

A

light, endurance training regimen may be useful to counteract the age-correlated satellite cell decrease therefore help retain muscle

41
Q

What is the role of mechano growth factor (IGF subtype)

Extra reading - Yang 2002

A

Activation and proliferation of satellite cells

42
Q

What is the role of IGF-IEa (IGF subtype)

Extra reading - Yang 2002

A

Differentiation of the proliferated satellite cells

43
Q

What is the role of HGF in satellite cells

EXTRA READING - Allen 1995

A

HGF is released during muscle injury

Causes satellite cell proliferation

44
Q

How does FGF-6 play a role in satellite cells

EXTRA READING - Floss 1997

A

FGF-6 knockout in mice has impaired satellite cell proliferation and a subsequent defect in muscle regeneration in response to a crush injury.

45
Q

How are satellite cells formed?

A

Formation of the muscle involves progression of precursor cells through different stages of development:

determination-> quiescence
-> proliferation-> differentiation

Intercal - Adaption in physiology (11 decks)

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