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 be revealed by transplantation experiments

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

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

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

Mario Cappechi Oliver Smithies ES cells can be used To manipulate the genome of the mouse but that’s a story for another day

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” Day 6-8: Cultures have attached & undergone differentiation Phase 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” Day 6-8: Cultures have attached & undergone differentiation Phase 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

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) 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) now Soon? Farther off Examples of ways stem cells might be used to treat disease:

Little support Wide-spread support The views of the scientific community Reproductive cloning is viewed by essentially all scientists as a procedure that is unwise for Scientific and ethical reasons Continuing and expanding research using mouse and human embryonic stem cells is strongly supported 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.

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 Other alternatives?

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