Lecture #10 Flashcards
what are five characteristics of adult stem cells?
- cells that are undifferentiated
- they can self renew and differentiate to become more specialized
- maintain cell populations facing neuronal death
- help healing
- counteract the aging process
what is homeostasis?
the ability to regulate internal conditions in organs or tissues, usually acting on several mechanisms that are under the control of feedback signals
how can you demonstrate the stemmwness of a single element?
clonogenic assay
if you compare the number of neurogenic niches along evolution, what do you see?
we can observe a substantial reduction in number
in mice what happens to young neuroblasts migrating through the RMS when they are in proximity to the OB?
they can leave the stream in all directions and enter the glomerular (GL) and the peri-glomerular (GLC) layers where they finish the complete differentiation into inhibitory neurons
what are generated by the sub ventricular zone, and why are they important?
inhibitory neurons - if they’re absent in the OB the mouse cannot sense the external environment
what niche can be found in the adult hippocampus?
the subgranular zone of the dentate gyrus
what is the subgranular zone of the dentate gyrus?
a small region in the medial part of the brain were we have a particular subset of NSCs
what do the cells in the subgranular zone of the dentate gyrus differentiate into?
progenitors that migrate hundreds of microns before starting the final differentiation into excitatory neurons
describe the type II cells in the subgranular zone:
intermediate progenitors that can undergo one or two rounds of cell proliferation before their final differentiation into type III cells
describe type III cells in the subgranular zone:
similar to neuroblasts - start to extend their axons and dendrites acquiring the full characteristics of a neuron → at the end they will integrate into the dendrite gyrus where they are very important for hippocampal functionality
what is the key difference between cells of the SVZ and the hippocampus?
SVZ: adult NSCs differentiate into GABAergic and some dopaminergic interneurons (both inhibitory neurons)
hippo: NSCs differentiate into excitatory neurons
describe the three types of dendate gyrus neurons:
type I: truly NSCs
type II: intermediate progenitor cells the can make some rounds of proliferation and then finally differentiate
type III: neuroblasts - cannot proliferate but have not completed maturation
describe the three types of cells in the SVZ:
type A: neuroblasts (immature neurons)
type B: NSCs
type C: iPSCs
describe the niche in the dendate gyrus (DG):
NSCs are in close contact with vascular epithelial cells astrocytes, and type III cells that differentiate into glutamatergic neurons
describe the niche in the SVZ:
the ependymal layer forms a sort of “floor” that separates the niche from the ventricular cavity → there’s a complex vasculature which is fundamental for the regulation of the neurogenesis in the niche and there are also astrocytes to support this niche
what do B cells of the SVZ express?
markers that are shared wit astrocytes - GFAP (typically associated with activated astrocytes)
describe the projections B cells of the SVZ can send:
can extend very short cytoplasmic bundles the enter between the ependymal cells and can imitate contact with the cerebrospinal fluid
they can also extend very long cytoplasmic bundles the enter in contact with the blood circulation surroinding the niche
what is the function of the type B cells of the SVZ?
they can sense at the same time what is inside the CSF and what is circulating in the blood → forms part of the BBB and interacts with the ventricular cavity
describe the type C cells of the SVZ:
lose their GFAP positivity and start to proliferate - after 2-3 rounds the differentiate into type A cells and leave the SVZ along the RMS
describe microglia in the SVZ:
uniformly distributed and its role in regards to the regulation of NSCs is still unknown - professor thinks maybe for cell proliferation
when observing the formation of NPCs, what was seen after embryonic day 12.5-13?
after symmetric cell division some neuroepithelial cells became quiescent and they stayed in this quiescent state for the entire embryonic life → then they start to acquire proliferative capacity when the brain will be an adult, becoming the NSCs of the SVZ
which neuroepithelial cells will become the lateral ventricle?
neuroepithelial cells in the lateral embryonic eminence
which neuroepithelial cells will become the dorsal part?
neuroepithelial cells entering G0 during the embryonic life
what cells will generate NSCs belonging to the septum?
cells in the hippocampal region will generate NSCs belonging to the medial part of the brain
what do neuroepithelial cells that undergo asymmetrical division become?
quiescent, and soon after they start to proliferate in the adult brain differentiating into ependymal cells
in the adult brain, what is the ventricular cavity separated from the individual niche by?
ependymal cells
describe the leakage in the ventricular and sub- ventricular zones, depending on the distribution of B cells and types of astrocytes end feet:
in the normal BBB, the is. first layer of cells, then pericytes, and then the end feet of astrocytes - in the SVZ the astrocytes can’t completely cover the vessel with their end feet, so in these regions the vessels are free from the end feet terminals creating a sort of leakage (possibility to detect the bur dye outside of the capillaries in the tissue)
demonstrates that if we have something toxic in the blood the signal can escape in the brain into the germinal niche and influence the capability of neural stem cells to proliferate and differentiate
what do asymmetric divisions of NPCs generate?
there is the generation of a NSC and a committed cell (a cell that will be differentiating)
what do symmetric divisions of NPCs generate?
two identical daughter cells - one is fated in the next round of cell division to make a symmetric cell division, the other is fated in the second round of cell division to differentiate
what percentage of neuroepithelial cells are fate to divide in a symmetrical way?
20% - the other 80% generate cells that are fated to terminal differentiation
why does aging occur?
our NSCs are disappearing, not only because our differentiated cells are dying
what is used to track neurogenesis in the brain, but what are some of its downsides?
Bromodeoxyuridine (BrdU) - uses S phase tracers to track NSCs
cons:
- can cause the death of B type cells if there is too much
- markers of synthesis not proliferation
- toxic
describe the morphological differences in the human SVZ niche and that of the mouse:
although both germinal niches are placed in regions flanking the lateral ventricle, in humans there is a layer of ependymal cells and then a gap of free space, then after that there are astrocyte that could belong to the NSCs
what can be used for immunohistochemistry that is expressed by migration neuroblasts during the embryonic life and by type A cells that leave the SVZ in rodents?
doublecortin (DCX)
what is a gliophiic marker typically associated with astrocytes but also type B cells used for immunohistochemistry?
vimetin
describe the neurogenetic niche as development occurs:
the initial post-natal neurogenesis can supply the brain with cortical neurons, but also neurons in the medial migratory stream → this is only transient because after one year the neurogenetic niche disappears
NSCs are only of a limited number in the brain
when are the vast majority of neurons in the brain generated?
during embryonic life
are there NSCs in the adult brain?
we don’t know
