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Stem Cells Week 12 Lecture Notes
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NEURAL STEM CELLSEvidence 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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