CSB349L19 - CSB349 Lecture 19 Reprogramming: Induced...

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CSB349 Lecture 19 November 24 th Reprogramming: Induced pluripotent stem cells Somatic cell nuclear transfer in mammals---prove you can reprogram a nucleus from a later stage animal. One result in mouse showed the best microenvironment that is permissive for reprogramming is the egg cytoplasm. What in the cytoplasm makes this easy? They did experiments in zygote hosts but it doesn’t work as well, but it is possible when the zygotes are isolated at a specific stage of mitosis. As in amphibians, donor nuclei from mammalian stem cells are better for reprogramming. The ability to be reprogrammed gets worse as the cell gets more differentiated. There are under certain circumstances, ways to get fully differentiated cells to differentiate. ..may just be a technical issue for us. Embryonic and stem cell are more amenable. Dolly is first cloned mammal from a donor cell derived from an adult tissue. Cloning larger mammals might be useful. The efficiency of this procedure was lousy and the source of the tissue was highly regenerative (loads of stem cells in the tissue). Adult cell type used but it wasn’t clear if it was a differentiated cell or not. So experiments came around to discern differentiated cells and Tcell nuclei. One issue in animal cloning is epigenetic (imprinting) marks in the adult are not correct. Once you transplant and adult nucleus into the new cytoplasm, you get biallelic expression, the differentiation in the genes (methylation pattern changes), are gone. The imprinted genes are involved in early development of the animal and extra cellular growth (like the placenta). Differential methylation at the IGF2 factor. One copy must be turned off, the other on (mother off and methylated), in the cloned animals, both are on. Could you add methylation or is that too difficult? You can cure a mouse disease. w/ Rag2 mutation.
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Lecture 19 November 24 th Ethical and technical issues. The major advantage of proving experimentally of cloning occurs, shows that therepeauting cloning is possible. Stem Cell Nuclear Transfer. Use cells as donor nuclei. If there are eggs available (take them from IVF clinics). Main ethical issue that people can’t get around is that you’re creating a human life (if your definition is at fertilization), just so you can kill it to extract cells. A blastiscist in a petri dish will not develop into a human unless it’s in a uterus. The potential health benefit is unknown. We don’t know it will work it humans, we only know it will
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This note was uploaded on 12/03/2010 for the course CSB CSB349 taught by Professor V.tropepe,a.moses during the Fall '10 term at University of Toronto- Toronto.

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CSB349L19 - CSB349 Lecture 19 Reprogramming: Induced...

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