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Stem Cells Week 12 Lecture Notes

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Lecture notes from week 12

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  • June 20, 2023
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  • 2022/2023
  • Lecture notes
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  • Week 12
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NEURAL STEM CELLS



Evidence for Postnatal Neurogenesis
 Until the 1950’s there was no way of measuring proliferation other
than observing mitoses
 1960’s Tritiated tymidine (3H-TdR) was first applied to adult brain
 Joseph Altman observed labelling in cortex, hippocampus and
olfactory bulb of adult rats
 His work was ignored for 40 years!


Newly Generated Cells in Adult Macaque Dentate Gyrus
 1997-99 Fred Gage and coworkers used BrdU and cell-type markers to evaluate neurogenesis in
animal models
 Neurons in the dentate gyrus express NeuN
 TuJ1-positive cells in the SGZ
 1999 Kornack & Rakic showed neurogenesis with BrdU incorporation and cell-specific markers in
dentate gyrus of adult macaque


Dynamics of Hippocampal Neurogenesis in Adult Humans
o Nuclear-bomb-test-derived 14C in human hippocampal neurons reveals adult neurogenesis
o The annual turnover rate is 1.75% (700 new neurons in each hippocampus per day)
o The extent of adult neurogenesis is comparable in middle-aged humans and mice




Adult Neural Stem Cell Niches
 NSCs primarily differentiate into neurons,
astrocytes, and oligodendrocytes, depending on
environmental cues
 Potential of using NSCs to treat central nervous
system diseases, including Parkinson’s and
Alzheimer’s disease.
 More recently, induced pluripotent stem cells
(iPSCs) have been proposed as an alternative
efficient method of generating neural stem cells.


Location of CNS stem and progenitor cell niches
 In the adult brain, neural stem cells (NSCs) exist principally in two regions.
 The SVZ of the lateral ventricle and the SGZ of each hippocampus (Kriegstein and Alvarez-Buylla,
2009), where neurogenesis occurs continuously.




Subventricular Zone of the Brain
(a) V/SVZ (orange) adjacent to the lateral ventricles. B1 stem cells
(dark blue) exposed to signals from three compartments:
CSF/ependymal cell niche (apical)
Intermediate SVZ niche
Perivascular niche (basal)
Ependymal cells (grey)

, Stem cells (dark blue)
Transit amplifying cells (green)
Neuroblasts (red).
Astrocytes (light blue)
Long distance axon terminals (purple).
Endothelial cells (pink)
Pericytes (yellow)
(B) B1 stem cells (green) have a polarized radial morphology and extend a long basal process that contacts
the vasculature (red).




Fate of Migrating Neuroblasts
- Postnatal neuronal precursors (grey) generated in the SVZ migrate
to the olfactory bulb (OB) and give rise to GABAergic OB neurons
- When homeostasis is disrupted (via the listed possibilities), SVZ
neuroblasts invade the parenchyma and adopt different fates



B1 Cells Decline Over Time
The majority (∼80%) of B1 cells becomes consumed by the
generation of type C transit amplifying cells (green), leading
to a declining B1 cell population as the animal ages




Generation of new neurons in the Subgranular Zone
(SGZ) of the adult Hippocampus
• The dentate gyrus of the hippocampus continues generating
new neurons throughout life.
• These neurons originate from radial astrocytes within the
subgranular zone (SGZ)

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