Lecture 30 - Metabolic reprogramming of skeletal muscle stem-cells Flashcards Preview

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Flashcards in Lecture 30 - Metabolic reprogramming of skeletal muscle stem-cells Deck (24)
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1
Q

True or False

In quiscent SCs you wont see the volume of mitochondria and the complexity of the network as opposed to active SCs

A

true

2
Q

Glycolysis produces intermediates which can be used for what?

what cycle is it?

A

New biomass for proliferating cells

Pentose cycle:

  • producing nucleotides for DNA
  • producing phospholipids (essential for membranes)
  • AAs - serine, glycine, cysteine
3
Q

There were approx 3000 genes that were heavily enriched in quiescent satellite cells. meaning upon activation of Satellite cells they were turned off or downregulated. what would these genes be responsible for?

what else has been found in activated SCs?

A

FA metabolism!. as well as cell adhesion and homeostatic processes

3000 genes that were upregulated in activated SCs. these were needed for:
- glucose metabolism!
-cell proliferation
cell cycle progression

4
Q

Is glycolysis happening in the quiescent state?

A

yes, but at very low/basal levels.

once active there is a huge increase - most being used to support the generation of new biomass

5
Q

histone acetylation does what for transcription?

A

increases transcription

6
Q

H4K16ac is an indicator of …

A

an activated satellite cell

7
Q

true or False

SirT1 requires NAD to work

A

true

deacetylates histones = represses transcription

8
Q

Does the total amount of SirT1 derease with satellite cell activation?

A

No.

doesn’t explain the increase in histone acetylation.

But NAD is required. and NAD levels are regulated through metabolism

9
Q

What happens to NAD levels from quiescent –> activated?

why?

A

NAD+ levels decrease

due to a rapid increase in glycolysis

this directly links the change in metabolism with the histone deaceylation

10
Q

describe the state of quiescent and activated SCs with respect to metabolism, NAD levels and SIRT1 activity

A
Quiescent
FA oxidation/oxphos
high NAD+
High SIRt1 activity
= transcriptional repression
Activated
Glycolysis
low NAD+
Low SIRT1 activity
= transcriptional activation
11
Q

true or false

The majority of proliferating SCs are MyoD+ and committed to the myogenic lineage

proliferating SCs are highly glycolytic

A

true

raises the question of whether they can be ‘‘pushed back’’ to a stem-like state by altering metabolism

12
Q

How can we test whether we can induce metabolic reprogramming?

A

culture media for proliferating cells

  1. control = glucose
  2. low glucose
  3. galactose (becomes energy neutral as it requires ATP to break down - this forces the cell into oxphos using pyruvate)

then measure cellular metabolism and genetic profile

13
Q

True or false

Glycolysis is increased in cells cultured in galactose

A

False

it is reduced.

forcing the cell to use oxphos

14
Q

true or false

inhibiting glycolysis with galactose decreases myogenic specification

A

true

15
Q

what is TXNIP?

A

an essential regulator of glycolysis

acts by inhibiting glucose uptake and conversion to glucose-6-phosphate (first step of glycolytic pathway)

16
Q

overexpression of TXNIP leads to what?

A

inhibition of glycolysis

complete stop of cell cycle and proliferation

decline in the expression of MyoD - pushes away from myogenic commitment

17
Q

G(0) cell state is referring to..

A

quiescence (reversible G0)

but there is also:

differentiation (irreversible G0)

Senescence (irreversible G0) - happens with age

18
Q

PKM1 does what?

A

Pryuvate kinase 1 - promotes movement of phosphoenolpyruvate (PEP) into pyruvate

19
Q

high levels of PKM1 is associated with increased reliance on..

A

oxphos

20
Q

PKM2 has a much ____ afinity for PEP

A

PKM2 has a much lower afinity for PEP

allows for the build up of PEP and the upstream intermediates

remember these are neccessary for the generation of new biomass

21
Q

PKM1 will have high levels in _____ cell population

PKM2 will have high levels in _____ cell populations

A

PKM1 will have high levels in quiscent cell population

PKM2 will have high levels in activated cell populations

22
Q

The difference between PKM1 and PKM2 is…

A

one exon

and quiescent cells have more of the PKM1 exon expressed

23
Q

true or false

overexpression of PKM2 in proliferating SCs blocks the production of lactate and decreases the rate of cell proliferation

A

false

overexpression of PKM2 in proliferating SCs blocks the production of lactate, but increases the rate of cell proliferation

24
Q

true or false

it is possible to reprogram previously commited/specified myogenic cells through targeted changes in metabolism

A

true

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