Neural Stem Cells

Question 1

Features of neural stems cells

Answer 1

Capacity for self renewal
Capacity to form differentiated progeny (itself/other cell types)

Question 2

Totipotent

Answer 2

Forms all lineages of the organism and extra embryonic tissue
Zygote/oocyte and early blastomeres

Question 3

Pluripotent

Answer 3

Forms all lineages of the body but no extra embryonic tissue
ES/inner cell mass of blastocyst

Question 4

Multipotent

Answer 4

Adult stem cells form multiple cell types of one lineage (haematopoietic cells)

Question 5

Neural stem cells examples

Answer 5

Neurons
Astrocytes
Oligodendrocyte and OPCs
Ependymal cells
NOT microglia

Question 6

Types of NSCs

Answer 6

Neuroepithelial cells form radial glia
Adult neural SC/radial glia like cells

Question 7

Where are radial glia located

Answer 7

Lateral ventricle

Question 8

Role of radial glia

Answer 8

Scaffold for neuroblasts
Divide to form neurons
1 RG and 1 N

Question 9

What do neural progenitors form

Answer 9

2 neurons

Question 10

Direct neurogenesis

Answer 10

RG to neuron

Question 11

Indirect neurogenesis

Answer 11

RG to NP to neurons

Question 12

What does the dentate gyrus (hippocampus) contain

Answer 12

Dense population of granule cells

Question 13

3 methods of proving neurogenesis

Answer 13

1) nucleotide analogues (NeuN/Brdu/DCX) markers
2) retrovirus during cell division
3) specific markers (transgenic mice have reported genes)

Question 14

2 major sites of neurogenesis

Answer 14

Subventricular zone SVZ
Subgranular zone SGZ

Question 15

Functions of NSCs in adult brain

Answer 15

OB - olfactory learning SVZ
Hippocampus- pattern separation
LV - SVZ neurogenesis forms glial cells

Question 16

What does the stem cell niche contain

Answer 16

NSC
Astroglia
Oligodendroglia
Neurons
Blood vessels (endothelial cells and pericytes)
ECM
Growth factors

Question 17

Role of C cells/IPC/transit amplifying cells

Answer 17

Divide rapidly
3/4 rounds then neurons

Question 18

What do neurogenic NSCs form

Answer 18

Astrocytes not oligodendrocytes

Question 19

GABAR in dentate gyrus

Answer 19

Adult:
GABAr open, Cl- in
Newborn:
GABAr open, Cl- out drives excitation

Question 20

What specifies the neuron

Answer 20

Regional origin determines subtype specification
Originates from RG

Question 21

2 models of specification

Answer 21

Maintained SC model (SC to neuron)
Set aside model (SC to SC to all neurons)

Question 22

What is quiescence

Answer 22

Reversible cell cycle arrest (G0 and G2)

Question 23

Roles of quiescence

Answer 23

Cells do not divide
Prevents exhaustion
Protects against DNA damage

Question 24

2 types of quiescence

Answer 24

DEEP - no dividing (similar morphology to Astrocytes)

SHALLOW - divided then return to quiescence, reduced metabolism

Question 25

Properties of active SCs

Answer 25

Lipid synthesis Oxidative phosphorylation Proteasomal activity

Question 26

What does active signalling use

Answer 26

Ascl1- drives SC activity Ins/GF1 mTOR (boosts protein synthesis)

Question 27

What does quiescent signalling use

Answer 27

NOTCH signalling (Receptors undergo cleavage) Hes1/5 (inhibits ascl1) Id4 (inhibits differentiation) PTEN (inhibits mTOR and PI3K)

Question 28

What occurs with ageing

Answer 28

Increase in quiescence Prevents exhaustion of SC pool

Question 29

What does transcriptomics show

Answer 29

Similar cells end up in clusters (Astrocytes and radial glial)

Question 30

Astrocytes to new neurons (in-vitro) | Magnusson et al., 2016

Answer 30

Astrocytes IPCs/C cells/transit amplifying cells Neuroblasts New neurons

Question 31

What are cerebral organoids

Answer 31

Interface of in vitro (2D) and in vivo Resemble an organ

Question 32

Applications of cerebral organoids

Answer 32

Transcriptomics Disease modeling Drug screening Brain regional identity Electrophysiological identity Brain evolution

Question 33

What is the role of choroid plexus organoids

Answer 33

Contributes to CSF and CSF clearance

Question 34

Limitations to organoids

Answer 34

Not all cells types represented No cranium/meninges (contain immature cells which signal to the brain) Complex structures incomplete Difficult to study age related diseases /AD