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Stem Cells
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
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
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
• 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
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
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
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
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.
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
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
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
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.
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)

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BIO420 Chapter 05

  • 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)