Induced pluripotent cells and reprogramming

Question 1

What is the Continous Waddington epigenetic landscape model?

How is differentiation described by this model?

Answer 1

• Cells coming down the hill
• From a very UNDIFFERENTIATED ES cell state
• Into a valley that represents a DIFFERENTIATED state
• Cells cannot go back up the hill (requires a lot of energy)
• SO, differentiation is primarily DIRECTIONAL and goes from a stable state to another stable state

Question 2

Describe reprogramming using the epigenetic landscape model

Answer 2

Can take a FULLY DIFFERENTIATED cell and take it all the way up the hill to become a STEM CELL

This cell can then be turned into other cell types by being pushed to differentiate into different vallies in this landscape

Question 3

What is direct reprogramming?

Answer 3

Transdifferentiation:

Direct differentiation from one differentiated state to another

Question 4

What did John Gurdon do in the 60’s and 70’s?

Answer 4

Came up with the idea to take a differentiated cella and reprograme it

• Took cells from the intestine of a mature albino frog and took the nucleus out of these cells
• Transferred the nucleus into an enucleated egg of the same strain of frog
• Allowed the egg to develop into a blastocyst and implanted into an adult different stain

Saw:
- The frog gave a progeny that was mature ALBINO frogs

Question 5

What did John Gurdon conclude from his experiments?

Answer 5

• All genetic material that was present in the albino mature nucleus was STILL INTACT
• Although gene expression is change during differentiation, the genetic material is NOT lost
• Can be reversibly reprogrammed to give rise to a whole mature organism