Neural Stem Cells

Question 1

What are neural stem cells?

Answer 1

Self-renewing multipotent cells with the potential to produce all major CNS lineages, including neurons, astrocytes, and oligodendrocytes

Question 2

Give 3 ways of studying mouse neural stem cells

Answer 2

Monolayer culture, 3D neurosphere culture, ex vivo transplantation

Question 3

Describe the process of early embryonic development

Answer 3

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

Question 4

What does the neural tube develop from?

Answer 4

Neural plate

Question 5

What does the peripheral nervous system develop from?

Answer 5

Neural crest cells

Question 6

Describe CNS development after closure of the rostral neuropore (5-8 weeks post-fertilisation)

Answer 6

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

Question 7

Why might neural progenitor cells not be stem cells?

Answer 7

They might not self-renew

Question 8

State a marker of mouse neural progenitor cells

Answer 8

Olig2

Question 9

Name 3 factors in the neuron vs glia fate choice

Answer 9

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

Question 10

Name a factor which promotes neuronal differentiation and inhibits glial differentiation

Answer 10

Neurogenin

Question 11

Name a co-activator which can alternately promote neuronal or glial differentiation

Answer 11

CBP/p300

Question 12

What does CBP/p300 bind to to promote glial differentiation?

Answer 12

STAT1/3

Question 13

What does CBP/p300 bind to to promote neuronal differentiation?

Answer 13

Ngn-E-protein complex

Question 14

State cell-intrinsic determinant of astrocyte differentiation

Answer 14

DNA methylation

Question 15

Who first proposed adult neurogenesis, and when?

Answer 15

Altman, 1960s

Question 16

Who first confirmed that neurogenesis could occur in adult animals?

Answer 16

Nottebohm et al, early 1980s, in the hippocampus of adult songbirds

Question 17

Name the 2 regions in which neural stem cells are found in the adult human brain

Answer 17

Subventricular zone of the lateral ventricles, subgranular zone of the hippocampal dentate gyrus

Question 18

State some requirements of the stem cell niche

Answer 18

Blood vessels, astrocytes, endothelial cells, basal lamina, ependymal cells

Question 19

State some molecular signals in the stem cell niche

Answer 19

VEGF, FGF, EGF, BDNF, SHH

Question 20

Can neural stem cells generate new cells outside of their niche?

Answer 20

No - transplantation studies have shown that neural stem cells fail to generate new neurons in non-germinal regions

Question 21

Describe the progress of neurogenesis in the subventricular zone

Answer 21

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

Question 22

What percentage of stem cells self-renew? (Obernier et al, 2018)

Answer 22

20% - 80% differentiate into new neurons

Question 23

Describe the results of the first human clinical trial of induced pluripotent stem cell transplantation

Answer 23

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

Question 24

Describe the progress of neurogenesis in the subgranular zone

Answer 24

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