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Summary NWI-BM073 Trends in stem cell biology + key questions
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Week 1 Ethical modelsEthical subjectivism is the idea that moral opinions are based on our feelings and nothing
more. In this view, there is no such thing as ‘objective’ right and wrong.
Consequentialism: the rightness/wrongness of an action is determined by its
consequences. Action → result
Example: utilitarianism, the right action is the one that promotes the greatest happiness of
the greatest number (maximizes social utility).
Example: ethical egoism, the right action is the one that promotes the greatest happiness
of the agent (maximizes the agent’s utility)
Deontology: The rightness/wrongness of an action is determined by inherent
features of the action itself, or by an inherently valid rule. Rule → action
If an action is of the wrong kind, it is forbidden, no matter how good its consequences are.
Rejects both Utilitarianism and Ethical Egoism. “The end doesn’t justify the means.”
Example: Kantianism, right actions must be universalizable and must treat rational agents
as ends, not mere means (trade-offs forbidden).
→ Universalizability: must be possible to will the principle of your action for everybody
without inconsistency. Lying violates universalizability because lying presupposes and
exploits a general practice of telling the truth.
Virtue Ethics: The rightness/wrongness of an action is determined by the character traits it
expresses. Emphasize what kind of person you should be. Character → action
Virtue-ethicists tend to side with deontologists against consequentialists – though not always
Divine command ethics
What makes an action right is the fact that God commands it (as opposed to the view that
God commands things because they are right already).
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, Week 3 Embryonic stem cells
LE: Epigenetics and pluripotency in mouse embryonic stem cells
Stem cells are biological cells that can differentiate into other types of cells and can divide
to produce more of the same type of stem cells (self renewal).
→ In mammals, there are two broad types of stem cells: embryonic stem cells,
which are isolated from the inner cell mass of blastocysts, and adult stem cells.
Different forms of cell potency during development in vivo
During cell development embryonic stem cells lose their potency, so their effectiveness. The
Inner Cell Mass stage (ICM) already contains two defined, irreversible cell populations.
In the blastocyst three axes can be defined: the embryonic-abembryonic (abemb-emb); the
animal-vegetal (an-veg); and a third axis on the same plane but perpendicular to the an-veg
axis. ICM stage already contains two defined, irreversible cell populations
→ Inner cell mass will form the fetus.
→ Inner cell mass cells can’t form the placenta anymore, and have lost their
potency.
→ Trophectoderm will become the placenta.
Inner cell mass can’t form the placenta and the trophectoderm can’t form the fetus, they lose
potency.
During gastrulation an embryo forms layers from ectoderm, endoderm and mesoderm.
- Ectoderm: is the outermost germ layer in animals. It gives rise to the skin, nervous
system, and sense organs. In the early embryo, it is the first layer to form from a
fertilized egg.
- Endoderm: is the innermost germ layer of eumetazoan embryos, surrounded by
mesoderm and ectoderm.
- Mesoderm: is the middle developmental layer between the ectoderm and endoderm,
which gives rise to the skeleton, muscle, heart and bones.
Ectoderm can’t get mesoderm anymore for example. During further differentiation, all ~200
cell types emerge.
Totipotency: Trophoblast and Inner Cell Mass
(not necessarily the most interesting cells; can also
form extraembryonic tissue). Totipotency is at the
basis of the whole cascade.
Embryonic stem cells
Pluripotency: Capable of differentiation into all
three germlayers (ecto-, endo-, and mesoderm)
Adult stem cells
Multipotency: Progenitor cells (hematopoietic
stem cell)
Oligopotency: e.g. myeloid stem cell (not
lymphoid lineage)
Unipotency: differentiate into one cell only
2
,Most interesting stage is the pluripotent stage where the fetus starts developing from a
clump of cells.
Waddington’s landscape: a cell begins at the bottom of a single potential well,
and then as development proceeds the one well successively splits into many
more, representing the possible differentiation states of the cell. For example
from a totipotency state to a unipotency state. → Cells lose potency during
development
Different pluripotent cells in vitro (mouse)
Pluripotent stage takes in mice 3-6 days to specialize and become ectoderm etc. Three
origins of pluripotent mouse cells:
- ESC = embryonic stem cells, early pluripotent cells. These cells can not become a
placenta anymore, they can only become EpiSC cells (red). That can become
ectoderm, endoderm or mesoderm.
- EpiSC = epiblast stem cells, late pluripotent state. They are depending on different
growth factors, like ActivinA of FGF2.
- EGC: enteric glial cells, after the epiblast stage they also take the cells to grow them.
The EGC stage. These cells are also pluripotent.
Embryonal carcinoma (EC) cells are the stem cells of teratocarcinomas, and the malignant
counterparts of embryonic stem (ES) cells derived from the inner cell mass of blastocyst-
stage embryos, whether human or mouse.
We call these embryonic stem cells pluripotent because of their self renewal and their
capability to differentiate. Can be tested with different experiments, see below.
3
, Test for pluripotency for newly derived cell lines
Mouse:
- Multilineage differentiation in vitro / vivo (Germline colonization)
- Extensive proliferation in vitro under well-defined culture conditions
- Known marker genes/ proteins (Oct4, Nanog, Sox2, SSEA, etc)
In practice these contribute to all somatic lineages/produce germ lines (chimerism) and
teratomas for absolute proof.
Teratocarcinoma is a form of malignant germ cell tumor that occurs in both animals and
humans. These tumors comprise an undifferentiated embryonal carcinoma (EC) component
and differentiated derivatives that can include all three germ layers.
Human:
- Multilineage differentiation in vitro (/ vivo NOT!) (Germline colonization)
- Normal, stable karyotype
- Extensive proliferation in vitro under well-defined culture conditions
- Known marker genes/ proteins (Oct4, Nanog, Sox2, SSEA, etc)
Conclusion: ES cells, like some other in vitro cultured cells, are pluripotent.
Application of ES cells
ES cells are the only ones that will form the complete body. Also ES cells can be used for
modeling the embryonic development in for example regenerative medicine.
An egg cell gets fertilized and forms an embryo and this embryo divides. The blastocyst is
formed with an inner layer of pluripotent cells. The cells from the inner cell mass can be
cultured on a disc and made to for example heart cells, nerve cells or pancreas cells. These
cells can cure several diseases like diabetes in combination with the pancreas cells.
Also lost cells can be replaced with (embryonic) stem cell therapies:
- Replace lost cells, might be useful in:
- Stroke (heart attack) -> loss of muscle cells
- Duchenne muscular dystrophy -> muscle degeneration (eventual death)
- Parkinson’s disease -> loss of dopamine-generating cells in the substantia nigra, a
region of the midbrain)
- Alzheimer
Dangers:
- Graft rejection (but not when it’s from the patient itself!; cord blood!)
- Graft-versus-host
- Teratocarcinoma
So ES cells are very useful for regenerative medicine and to study embryonic development.
Regenerative medicine is the process of replacing or "regenerating" human cells, tissues or
organs to restore or establish normal function.
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