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Stem cells (and how to make your own). Mr Dare TSI Friday Feb 11 1.30 in S1. What are stem cells?. What can they do?. 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. - PowerPoint PPT Presentation
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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