Chapel Hill- its
a great place to learn about
science!
How does
a fertilized
egg become
an
animal?
Clam egg and sperm: ECB Fig. 20-3
Ain’t I
Amazing!?
In the adult, most cells are
specialized for specialized tasks
Red blood cells carry oxygen
Neurons trasmit electrical signals
Pancreatic islet cells secrete insulin
We say these cells are
terminally differentiated
Red blood cells carry oxygen
Neurons trasmit electrical signals
Pancreatic islet cells secrete insulin
However, within most tissues,
tissue stem cells retain the potential
to make several
different cell
types
An example of tissue stem cells:
the blood cell lineage
Tissue stem cells are already used
to treat disease
A bone marrow transplant involves
transferring stem cells to a recipient
whose stem cells
were killed
Tissue stems cells are “multipotent”
i.e., their descendents
Can do several
different things
But they are NOT “totipotent”
i.e., their descendents
Do not contribute to
Other tissues
However, the
descendents of
a fertilized
egg can
become
ALL cell types
in an
animal.
Clam egg and sperm: ECB Fig. 20-3
One simple view of embryonic development:
One cell becomes many and
Different cells choose different fates
As a result, as development proceeds
and cells make choices
their developmental potentials become
more and more limited
The
choices cells
make
can
Determination
can be
assayed
by be
transplantation
experiments
revealed by
transplantation
experiments
Early gastrula
Cells alter their fate
to match that of
neighbors
i.e. not determined
Transplant
nervous system
to epidermis
and vice versa
Late gastrula
Cells retain their
original fates,
regardless of
neighbors
i.e. determined
Cloning:
The ultimate
Transplant
experiment
Dolly
Cloning:
The ultimate
Transplant
experiment
Oops-Here’s the real Dolly
(guess which tissue
she was cloned from!)
Cloning:
The ultimate
Transplant
experiment
So HOW
does
reproductive
cloning work?
Blastula stage cells
Can be easily re-programmed
But cloning success drops dramatically as
the age of the nuclear donor increases
Gilbert Fig. 4.6
So is reproductive cloning a good idea?
Gilbert Fig. 4.6
Remember this: blastula stage cells
Can be easily re-programmed
Enough about frogs: what about humans?
What happens during early human development?
Inner cell mass
Embryos develop to the blastocyst stage
before implantation
(Day 6)
Gilbert Fig. 11.26
Gastrulation
& all later events
occur within the
mass of
extraembryonic
tissue
Gastrulation finished by Day 21
Week 4: Neurulation, bone, muscle
Week 6: Most major organs present
The mouse provides a superb model for
human development and disease because
we share virtually ALL of our genes
and use them in similar ways
Blastocyst stage cells
can be easily
incorporated
into a different
blastocyst stage
embryo leading
to production
of chimeras
A mouse with
“3 parents”
Gilbert Fig. 11.38
Blastocyst stage cells
Are thus totipotent;
In other words their
descendents can
become every
cell type
What are
Embryonic stem cells?
Blastocyst-stage cells
that have been coaxed
and coddled into
growing in culture
Source: Genetic Science Learning Center
at the Eccles Institute of Human Genetics
The University of Utah
Embryonic
stem cells can be
grown in a dish
and then incorporated
into an embryo.
Their descendents
can contribute to
ALL tissues
ES cells can be used
Recipe to "knockout" a gene:
Step 2
To manipulate the
genome of the mouse
but that’s a story
for another day
A normal cell has
two copies of gene
X
mRNA
Gene X
mRNA
Mario Cappechi
Gene X
Scientists use magic tricks to insert gene for
resistance to the drug neomycin into the middle
of one of the copies of gene X,
destroying its function.
Neo resistance gene
No
mRNA
Gene X
mRNA
Gene X
Oliver Smithies
Current human
embryonic stem lines
were derived from
blastocyst-stage
human embryos
that were created
for in vitro fertilization
and not used
Source: Genetic Science Learning Center
at the Eccles Institute of Human Genetics
The University of Utah
In theory, human
embryonic stem lines
could also be created by
“therapeutic cloning”,
Thus making them
a perfect match
for the donor
Source: Genetic Science Learning Center
at the Eccles Institute of Human Genetics
The University of Utah
ES cells can differentiate in culture
Day 0: Separate cells
And let grow into “embryoid bodies”
Day 3: Plate EBs & let them attach
To dish in “differentiation medium”
Phase
Day 6-8: Cultures have attached
& undergone differentiation
In red is a marker for blood vessels
The cell types produced vary depending on the culture conditions
Day 0: Separate cells
And let grow into “embryoid bodies”
Day 3: Plate EBs & let them attach
To dish in “differentiation medium”
Phase
Day 6-8: Cultures have attached
& undergone differentiation
In red is a marker for blood vessels
What if we could:
Culture ES cells one way to
Make dopaminergic neurons
Culture ES cells a different way to
Make muscle stem cells
And culture ES cells a third way to
Make pancreatic islet cells
Examples of ways stem cells
might be used to treat disease:
now
Soon?
1. Parkinson’s disease: Implant stems cells that had
been coaxed into being dopamine producing neurons
(this is being tested with fetal cells today)
2. Type I Diabetes: Implant stem cells that had
been coaxed into being insulin-producing islet cells
(islet transplants have been done, but stem cells
are not yet available)
Farther
off
3. Implant stem cells to repair heart damage
(experiments being tried in the mouse)
4. Implant stem cells to repair spinal cord injury
(Many hurdles lie ahead)
The views of the scientific community
Little
support
Reproductive cloning is viewed by essentially all
scientists as a procedure that is unwise for
Scientific and ethical reasons
Wide-spread Continuing and expanding research using mouse and
human embryonic stem cells is strongly supported
support
by most scientific societies and individual scientists
The law
On August 9, 2001 President Bush
announced that he would permit Federal funds
to be used only for research with
human embryonic stem cells
derived before August 9, the date of his speech
The flaws
Some of the cell lines were not really ES lines
Others are unavailable for proprietary reasons
Others are genetically defective
“16/78 lines have died
31/78 belong to foreign labs that will not
Provide them to US researchers
7/78 are duplicates of other lines
8/78 are not currently available
Of the remaining lines, some have “severe
Genetic abnormalities”
Gillis/Weiss, Washington Post, 3/3/2004
What are examples of groups
That want changes
in the current guidelines?
American Medical Association
American Society for Cell Biology
Association of American Medical Colleges
American Association for the Advancement of Science
Juvenile Diabetes Research Foundation
Christopher Reeve Paralysis Foundation
National Council on Spinal Cord Injury.
Other alternatives?
Source: Genetic Science Learning Center
at the Eccles Institute of Human Genetics
The University of Utah
Other alternatives?
Source: Genetic Science Learning Center
at the Eccles Institute of Human Genetics
The University of Utah
Some research suggests
Adult stem cells can be
coaxed into changing fate in culture
Can I be coaxed
Into making neurons
Or cardiac muscle?
The ideal situation is to
use a patient
as their own donor,
eliminating issues
of transplant rejection
Source: Genetic Science Learning Center
at the Eccles Institute of Human Genetics
The University of Utah
Do you want to learn more?
Check out the website of
The Genetic Science Learning Center
at the Eccles Institute of Human Genetics
The University of Utah
http://gslc.genetics.utah.edu/units/stemcells/