Neural Stem Cells Flashcards
Features of neural stems cells
Capacity for self renewal
Capacity to form differentiated progeny (itself/other cell types)
Totipotent
Forms all lineages of the organism and extra embryonic tissue
Zygote/oocyte and early blastomeres
Pluripotent
Forms all lineages of the body but no extra embryonic tissue
ES/inner cell mass of blastocyst
Multipotent
Adult stem cells form multiple cell types of one lineage (haematopoietic cells)
Neural stem cells examples
Neurons
Astrocytes
Oligodendrocyte and OPCs
Ependymal cells
NOT microglia
Types of NSCs
Neuroepithelial cells form radial glia
Adult neural SC/radial glia like cells
Where are radial glia located
Lateral ventricle
Role of radial glia
Scaffold for neuroblasts
Divide to form neurons
1 RG and 1 N
What do neural progenitors form
2 neurons
Direct neurogenesis
RG to neuron
Indirect neurogenesis
RG to NP to neurons
What does the dentate gyrus (hippocampus) contain
Dense population of granule cells
3 methods of proving neurogenesis
1) nucleotide analogues (NeuN/Brdu/DCX) markers
2) retrovirus during cell division
3) specific markers (transgenic mice have reported genes)
2 major sites of neurogenesis
Subventricular zone SVZ
Subgranular zone SGZ
Functions of NSCs in adult brain
OB - olfactory learning SVZ
Hippocampus- pattern separation
LV - SVZ neurogenesis forms glial cells
What does the stem cell niche contain
NSC
Astroglia
Oligodendroglia
Neurons
Blood vessels (endothelial cells and pericytes)
ECM
Growth factors
Role of C cells/IPC/transit amplifying cells
Divide rapidly
3/4 rounds then neurons
What do neurogenic NSCs form
Astrocytes not oligodendrocytes
GABAR in dentate gyrus
Adult:
GABAr open, Cl- in
Newborn:
GABAr open, Cl- out drives excitation
What specifies the neuron
Regional origin determines subtype specification
Originates from RG
2 models of specification
Maintained SC model (SC to neuron)
Set aside model (SC to SC to all neurons)
What is quiescence
Reversible cell cycle arrest (G0 and G2)
Roles of quiescence
Cells do not divide
Prevents exhaustion
Protects against DNA damage
2 types of quiescence
DEEP - no dividing (similar morphology to Astrocytes)
SHALLOW - divided then return to quiescence, reduced metabolism
Properties of active SCs
Lipid synthesis
Oxidative phosphorylation
Proteasomal activity
What does active signalling use
Ascl1- drives SC activity
Ins/GF1
mTOR (boosts protein synthesis)
What does quiescent signalling use
NOTCH signalling (Receptors undergo cleavage)
Hes1/5 (inhibits ascl1)
Id4 (inhibits differentiation)
PTEN (inhibits mTOR and PI3K)
What occurs with ageing
Increase in quiescence
Prevents exhaustion of SC pool
What does transcriptomics show
Similar cells end up in clusters
(Astrocytes and radial glial)
Astrocytes to new neurons (in-vitro)
Magnusson et al., 2016
Astrocytes
IPCs/C cells/transit amplifying cells
Neuroblasts
New neurons
What are cerebral organoids
Interface of in vitro (2D) and in vivo
Resemble an organ
Applications of cerebral organoids
Transcriptomics
Disease modeling
Drug screening
Brain regional identity
Electrophysiological identity
Brain evolution
What is the role of choroid plexus organoids
Contributes to CSF and CSF clearance
Limitations to organoids
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
