Transitions between cellular states - Induced pluripotent stem cells
4 important questions on Transitions between cellular states - Induced pluripotent stem cells
What are the 4 factors that induce iPS cell form fibroblasts?
Sox2
Klf4
MYC
(Eselbrug: OSKM)
iPS cell contribute to various germ layers, which indicate that iPS are not only pluripotent in vitro but also in vivo
Why is reprogramming iPS cells inefficient?
- Time consuming
- Only 1% of plated cells are able to become iPS cells
- Epigenetic barriers restrict reprogramming efficiency
Epigenetic barriers (chromatin structure)
- Normal (good, because your don't want your skin cell to spontaneously become a heart cell)
- Restrictive, difficult to get over the barrier for the cell and is therefore not able to leave the proliferative epistate (cancer)
- Epigenetic insult raises chromatin barrier
- Permissive, plasticity allows bidirectional transition
- epigenetic lesion lowers chromatin barrier
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What are the restrictive factor in reprogramming iPS cells ?
- Mbd3 is a member of NuRD-complex
- The NuRD-complex functions as a co-repressor complex
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