Stem cells Stem cells (and how to make your own)(and how to make your own)

Mr DareTSI Friday

Feb 111.30 in S1

What are stem cells?What are stem cells?

What can they do?What can they do?

Why can’t all our cells do this?Why can’t all our cells do this?

• Pluripotency genes are switched off• Why?• So you get…• How?• Epigenetics!

Transcription is controlled by chemically changing the DNA

• Transcription is controlled by promoter regions of DNA

• A protein called a transcription factor binds allowing transcription

• Promoter regions for pluripotency genes are turned off in two ways;

1 – methylating the DNA

• Genes are switched off by methylation of the DNA at the TF binding site

2 – wrapping the DNA around the histones more tightly

• DNA is negatively charged – keeping positive charges on the histones locks up the DNA

Acetyl groups remove the positive charge from the histones

So…So…• Our cells can’t

go back uphill• They lose

pluripotency – the master switches are turned off

• But is it gone for good?

Dr Shinya Yamanaka

New master New master switchesswitches

What effect did this have?What effect did this have?MEF cells – stem cells for skin

Mouse embryonic stem cell (MES) colony

The product – skin cells transformed into cells which are just like ES cells

But will they act like ES cells – will they have pluripotency?

• Question…Question…• What’s the best container for What’s the best container for

growing mouse cells?growing mouse cells?• Answer…Answer…

SCID mice with teratomas from injected transformed cells

So it looks like these cells are pluripotent

• These newly transformed pluripotent cells are called – Induced pluripotent stem cells– (or iPS cells for short)

• And we know we can get whole organisms from these iPS cells because…

Generation of ES cells

zona

Trophoectoderm Inner cell mass

ES cells are pluripotentialES cells provide the system where we are able to modify the genome

MAC3 ES cells

What if we stick cells back into an embryo?

ChimaerasiPS cells from black mouse

ES cells from white mouse

Return to pseudopregnant fosters

This mouse works! But can we get a whole mouse from iPS cells?

Great – can we do it with humans?Great – can we do it with humans?

• Yes! Here it is!

Human dermofibroblasts

(HDF’s)

Transformed HDF’s making colony just like

an ES cell colony

• We can now turn ordinary skin cells into…– Cardiac tissue– Liver cells– Muscle cells– Neural cells– Blood cells– Back into skin cells– http://www.youtube.com/watch?v=IjU81a5TjZs&f

eature=fvw

But there are some big problemsBut there are some big problems

• The pluripotency genes are turned off during development for a reason

• Mice produced from iPS cells very often died of cancer

• If you can find a safe way of using iPS cells therapeutically, you will win a Nobel prize