Neural Stem Cells Flashcards
Define the properties of stem cells Describe similarities and differences between pluripotent and tissue-specific stem cells Define the properties and localisation of neural stem cells in the CNS Discuss that neural stem cells are temporally and spatially regulated during development
What are neural stem cells?
Self-renewing multipotent cells with the potential to produce all major CNS lineages, including neurons, astrocytes, and oligodendrocytes
Give 3 ways of studying mouse neural stem cells
Monolayer culture, 3D neurosphere culture, ex vivo transplantation
Describe the process of early embryonic development
Fertilisation of an egg by a sperm leads to formation of a zygote. This goes on to form a blastocyst, which undergoes implantation and gastrulation. It can then differentiate into the three main ‘layers’ – ectoderm, endoderm, and mesoderm
What does the neural tube develop from?
Neural plate
What does the peripheral nervous system develop from?
Neural crest cells
Describe CNS development after closure of the rostral neuropore (5-8 weeks post-fertilisation)
3 primary brain vesicles are formed - prosencephalon, mesencephalon, and rhombencephalon. The prosencephalon splits to form telencephalon and prosencephalon, and the rhombencephalon splits to form the metencephalon and myelencephalon
Why might neural progenitor cells not be stem cells?
They might not self-renew
State a marker of mouse neural progenitor cells
Olig2
Name 3 factors in the neuron vs glia fate choice
1) Temporal/ spatial regulation by expression of neuronal or glial growth factors and transcription factors
2) Competing use of shared components in signalling pathways
3) Epigenetic regulation
Name a factor which promotes neuronal differentiation and inhibits glial differentiation
Neurogenin
Name a co-activator which can alternately promote neuronal or glial differentiation
CBP/p300
What does CBP/p300 bind to to promote glial differentiation?
STAT1/3
What does CBP/p300 bind to to promote neuronal differentiation?
Ngn-E-protein complex
State cell-intrinsic determinant of astrocyte differentiation
DNA methylation
Who first proposed adult neurogenesis, and when?
Altman, 1960s
Who first confirmed that neurogenesis could occur in adult animals?
Nottebohm et al, early 1980s, in the hippocampus of adult songbirds
Name the 2 regions in which neural stem cells are found in the adult human brain
Subventricular zone of the lateral ventricles, subgranular zone of the hippocampal dentate gyrus
State some requirements of the stem cell niche
Blood vessels, astrocytes, endothelial cells, basal lamina, ependymal cells
State some molecular signals in the stem cell niche
VEGF, FGF, EGF, BDNF, SHH
Can neural stem cells generate new cells outside of their niche?
No - transplantation studies have shown that neural stem cells fail to generate new neurons in non-germinal regions
Describe the progress of neurogenesis in the subventricular zone
Neural stem cells (B type) generate amplifying neural progenitors (C type), which form neural blast cells (A type). These blast cells migrate along a channel of astrocytes to the olfactory bulb, where they form interneurons with existing neurons
What percentage of stem cells self-renew? (Obernier et al, 2018)
20% - 80% differentiate into new neurons
Describe the results of the first human clinical trial of induced pluripotent stem cell transplantation
After transplantation into the eye, gene mutations were identified - none were in coding regions, but due to limited knowledge of non-coding regions the trial was stopped
Describe the progress of neurogenesis in the subgranular zone
Neural stem cells in the dentate gyrus develop into progenitor cells, which develop into immature neurons. These neurons migrate into the granule cell layer and integrate with axons in the CA3 region of the hippocampus
