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Stem cells (and how to make your own)

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.

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Stem cells (and how to make your own)

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  1. Stem cells (and how to make your own) Mr Dare TSI Friday Feb 11 1.30 in S1

  2. What are stem cells?

  3. What can they do?

  4. Why can’t all our cells do this? • Pluripotency genes are switched off • Why? • So you get… • How? • Epigenetics!

  5. 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;

  6. 1 – methylating the DNA • Genes are switched off by methylation of the DNA at the TF binding site

  7. 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

  8. So… • Our cells can’t go back uphill • They lose pluripotency – the master switches are turned off • But is it gone for good?

  9. Dr Shinya Yamanaka New master switches

  10. What effect did this have? But will they act like ES cells – will they have pluripotency? 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

  11. Question… • What’s the best container for growing mouse cells? • Answer…

  12. So it looks like these cells are pluripotent SCID mice with teratomas from injected transformed cells

  13. 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…

  14. Trophoectoderm Inner cell mass zona Generation of ES cells MAC3 ES cells ES cells are pluripotential ES cells provide the system where we are able to modify the genome

  15. What if we stick cells back into an embryo? Chimaeras iPS cells from black mouse ES cells from white mouse Return to pseudopregnant fosters

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

  17. 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

  18. 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&feature=fvw

  19. But 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

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