Chapel Hill- itsa great place to learn aboutscience!

How does a fertilized egg become

ananimal?

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 areterminally differentiated

Red blood cells carry oxygen

Neurons trasmit electrical signals

Pancreatic islet cells secrete insulin

However, within most tissues,tissue stem cells retain the potentialto make severaldifferent celltypes

An example of tissue stem cells: the blood cell lineage

Tissue stem cells are already used to treat disease

A bone marrow transplant involvestransferring stem cells to a recipientwhose stem cells were killed

Tissue stems cells are “multipotent”i.e., their descendentsCan do severaldifferent things

But they are NOT “totipotent”i.e., their descendentsDo not contribute to Other tissues

However, the descendents of a fertilized

egg can become

ALL cell typesin ananimal.

Clam egg and sperm: ECB Fig. 20-3

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 eventsoccur within the mass of extraembryonic tissue

What are Embryonic stem cells?Blastocyst-stage cellsthat have been coaxedand coddled intogrowing in culture

Source: Genetic Science Learning Center at the Eccles Institute of Human GeneticsThe University of Utah

Embryonic stem cells can be grown in a dish and then incorporatedinto an embryo.Their descendentscan contribute toALL tissues

Current human embryonic stem lineswere derived from blastocyst-stagehuman embryosthat were createdfor in vitro fertilizationand not used

Source: Genetic Science Learning Center at the Eccles Institute of Human GeneticsThe University of Utah

In theory, human embryonic stem linescould also be created by “therapeutic cloning”,Thus making thema perfect match for the donor

Source: Genetic Science Learning Center at the Eccles Institute of Human GeneticsThe University of Utah

What if we could:

Culture ES cells one way toMake dopaminergic neurons

Culture ES cells a different way toMake muscle stem cells

And culture ES cells a third way toMake 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?

Fartheroff

Examples of ways stem cells might be used to treat disease:

Littlesupport

Wide-spread support

The views of the scientific community

Reproductive cloning is viewed by essentially allscientists as a procedure that is unwise forScientific 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 lawOn 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 flawsSome of the cell lines were not really ES linesOthers are unavailable for proprietary reasonsOthers are genetically defective

“16/78 lines have died31/78 belong to foreign labs that will notProvide them to US researchers7/78 are duplicates of other lines8/78 are not currently available

Of the remaining lines, some have “severeGenetic abnormalities”

Gillis/Weiss, Washington Post, 3/3/2004

What are examples of groups That want changes in the current guidelines?

American Medical AssociationAmerican Society for Cell BiologyAssociation of American Medical CollegesAmerican Association for the Advancement of ScienceJuvenile Diabetes Research FoundationChristopher Reeve Paralysis FoundationNational Council on Spinal Cord Injury.

Source: Genetic Science Learning Center at the Eccles Institute of Human GeneticsThe University of Utah

Other alternatives?

Source: Genetic Science Learning Center at the Eccles Institute of Human GeneticsThe 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 neuronsOr cardiac muscle?

The ideal situation is to use a patientas their own donor,eliminating issuesof transplant rejection

Source: Genetic Science Learning Center at the Eccles Institute of Human GeneticsThe University of Utah

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

Oct3/4, Sox2, c-Myc, and Klf4

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

James Thomson

Science, Nov. 22 2007

Cell, Nov. 20 2007

OCT3, SOX2, NANOG and LIN28

1/10,000 cells reprogrammed

Shinya Yamanaka

1/5,000 cells reprogrammed

Then last week two labs repeated the trick with human cells!

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

Oct3/4, Sox2, c-Myc, and Klf4

Shinya Yamanaka

Kyoto JAPAN

ScienceJune 2006 + June 2007

Screen for genes expressed specifically by ES cells

24 genes

If all are mis-expressed inSkin cells, a small fraction

Take on properties of ES cells

Start eliminating genes: Ultimately find that these four can do the trick

In the past year two breakthroughs have changed the landscape

http://gslc.genetics.utah.edu/units/stemcells/

Do you want to learn more?

Check out the website of

The Genetic Science Learning Center at the Eccles Institute of Human GeneticsThe University of Utah