Lecture 4 - Adult Neural Stem Cells

Question 1

Adult Neural Stem Cells:

Answer 1

• Self-renewing
• Slow-dividing
• Remain undifferentiated and give rise to “transit amplifying progenitor” cells. which in turn generate neurons or glia
• Are referred to as “Astro-glial” cells, which express GFAP and Sox2
• Supply new neurons in many adult mammals (e.g. mouse, rat, monkeys)
• Adult stem cell populations are often heterogenous [They an be in different states of activity or dormancy and many have different roles in tissue homeostasis and regeneration]

Question 2

Major Sites of Adult Neurogenesis:

Answer 2

Adults NSCs are located mainly in 2 regions of the brain:

1. The dentate gyrus of the hippocampus
2. The lateral ventricle wall

Question 3

The Adult Neural Stem Cell Niche:

Answer 3

• Adult NSCs occupy complex cellular niches
• These niches expose NSCs and their immediate progeny (transit amplifying cells) to a wide range of influences, which maintain these cells and regulate their activity
• This includes feedback from differentiating progeny (neurons), signals and neurons from the associated blood vessels, and the activity of mature neurons
• The niches for NSCs in the lateral ventricle and hippocampus have differences as well as similarities

Lateral Ventricle:
B1 cells (Neural Stem Cell)
-> C Cells (Intermediate Progenitor Cells [IPCs])(Transit Amplifiers)
-> A cells (Neuroblasts = New born neurons)

Dentate gyrus of the hippocampus:
RA (Radial astrocyte = Neural Stem Cell)
-> IPC1
-> IPC2 
-> ICG (Immature Granule Cells)
-> Granule Cells

Question 4

Regulation of Adult Neural Stem Cells:

Answer 4

Growth Factors
Signalling Molecules
Neurotransmitters

All of the above regulate Adult NSCs and their transit amplifiers

Question 5

Regulation of Adult Neural Stem Cells:

Answer 5

• Growth Factors (e.g. Insulin growth factor 2/IGF2)
• Signalling Molecules (e.g. BMP antagonists “Noggin” and “Chordin”)
• Neurotransmitters (e.g. Dopamine and Serotonin)

All of the above regulate Adult NSCs and their transit amplifiers

Question 6

Effect of BMP signalling on Adult Neural Stem Cells:

Answer 6

• BMP signalling promotes hippocampal NSC quiescence
• Relief from BMP signalling allows NSCs to proliferate and generate new neurons. Neurons then up-regulate a different BMP receptor as they exit the cell cycle