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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.

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Stem cells (and how to make your own)

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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 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 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

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

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


Stem cells and how to make your own

So…

  • Our cells can’t go back uphill

  • They lose pluripotency – the master switches are turned off

  • But is it gone for good?


Stem cells and how to make your own

Dr Shinya Yamanaka

New master switches


What effect did this have

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


Stem cells and how to make your own

  • Question…

  • What’s the best container for growing mouse cells?

  • Answer…


Stem cells and how to make your own

So it looks like these cells are pluripotent

SCID mice with teratomas from injected transformed cells


Stem cells and how to make your own

  • 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…


Stem cells and how to make your own

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


Stem cells and how to make your own

What if we stick cells back into an embryo?

Chimaeras

iPS cells from black mouse

ES cells from white mouse

Return to pseudopregnant fosters


Stem cells and how to make your own

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


Stem cells and how to make your own

  • 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


But there are some big problems

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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