BIO420

1. Stem Cells

2. Stem Cell- a cell capable of creating further
cell which can become specialized cell.
• In other words, it is an unspecialized cell
• It can divide and recreate itself as well
Stem cells have potency- they can produce
many types of differentiated cells

3. Types of stem cell
division
• Symmetrical- the stem cell produces
wither two self-renewing stem cells or
two daughter cells that will commit to
specialization.
• The result is an expansion or
reduction in the total resident stem
cell population.
• Asymmetrical- a stem cell produces a
committed call and another stem cell.
This stabilizes the stem cell population.
This is a more common method
• A third type of division is where some
stem cells produce committed stem cells.
This is called the population asymmetry
mode

4. Potency Defines a Stem Cell
• Potency is defined by how many types of specialized cells a stem cell can make.
• Totipotent- produce all types. In mammals, the zygote and divisions up to 4-8 cells
are totipotent
• After this point, the embryo begins to form. The inner cells are pluripotent
meaning they can make all the cells of the embryo
• Multipotent- they generate cells specific to the tissue they are in.
• Adult tissues contain adult stem cells which are largely multipotent
• These cells are more restricted in the types of cells they can make. They are
also restricted in the number of generations they can produce

5. • When a multipotent cell divides asymmetrically, the committed
daughter cells go through a transitional stage as a progenitor
• A progenitor can only divide a few times and then must
differentiate

6. Stem Cell Regulation
• Since stem cells can self-renew and/or differentiate, how is this
tailored to fit the needs of the tissue?
• The environment around the stem cell is knows as the stem
cell niche
• There are principles of stem cell regulation that can be applied to
each environment. They can be classified into two types:
• Extracellular
• Intracellular

7. Extracellular Regulation
• Physical Mechanisms- There are physical things outside the cell the influence regulation
such as:
• Adhesion factors
• The cytoskeleton
• Cell density
• Chemical Regulation- proteins secreted from surrounding cells. These chemicals often
keep the cell uncommitted. When stem cells get further from the niche environment
they can start committing again

8. Intracellular Mechanisms
Regulation by Cytoplasmic Determinants- cells get partitioned during
cytokinesis. Factors regulating stem cell fate are distributed evenly among the
cells or they can be distributed unevenly
Transcriptional Regulation- transcription factor in the cell can keep it dormant
or proliferative
Epigenetic Regulation- this occurs at the chromatin. For example, histone
modification of gene expression

9. Pluripotent Cells in the
Embryo
• In animals, totipotent or pluripotent stem
cells eventually become progenitor cells.
However, in plants we find totipotent stem
cells at the shoot apex and the root apex
throughout the life of the cell.

10. Cells of the Inner Cell Mass
• After the zygote cleaves into a morula, it will
turn into a blastocyst
• A blastocyst contains a cavity
• There is an inner cell mass (ICM) and a layer
of cells surrounding it (and the cavity) called
trophectoderm Cells. The cavity is called
Blastocel
• The ICM will give rise to a layer of cells called
primitive ectoderm (which will be the yolk
sac)
• The epiblast will eventually become the
three germ layers (ectoderm, mesoderm,
and endoderm)
• How does the ICM stay pluripotent?
• Three transcription factors: Oct4, Nanog,
and Sox2 keep the cells uncommitted. As the
epiblast develops and differentiates, these
three factors lose their expression

11. Adult Stem Cell
Niche in Animals
As cells continue to
proliferate and differentiate in
adults, how are multipotent
stem cells controlled?
The next slide presents an
example

12. Adult Intestinal Stem Cell Niche
• The lining of our small intestine contain
villi. The valleys between two villi are
called crypts
• Cell generation happens in the crypts. Cells
lough off at the villi tips. Every two to three
days there is a turn-over of cells.
• Stem cells lie at the crypts. There is
asymmetrical division, so some cells
differentiate, and some remain as stems
cells.
• As progenitor cells rapidly differentiate and
move towards the tip, they go through
Anoikis. This is apoptosis due to loss of
attachment to other cells and the
basement membrane.
• The stem cells that remain in the crypt are
mixed with Paneth cells. This suggests that
those cells protect the stem cells

13. The
Mesenchymal
Stem Cell
The Multipotent
Mesenchymal Stem Cells
(MSC) have been found in
many adult tissues.
This suggests that they
have a large amount of
diversity of an adult
multipotent stem cell.

14. Stem Cell Research
It was thought that differentiated cells could not be reversed into stem
cells again
A 2006 study showed that inserting activated copies of four genes
could cause most any cell to become induced pluripotent stem cells.
• They would have potency similar to embryonic stem cells.
• These genes coded for transcription factors
• Sox2 and Oct4 (which block differentiation)
• C-Myc (opened up chromatin for transcription)
• Klf4 (prevents cell death)