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Chunk #5 — Efficiency of nuclear reprogramming

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Epigenetic factors influencing resistance to nuclear reprogramming.
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When somatic cell nuclei are transplanted to enucleated eggs (in second meiotic metaphase), the efficiency with which new cell types are generated decreases by over 10-fold, as the donor cells from which nuclei are taken become more differentiated (Figure 2a). For example, the proportion of total nuclear transfers to Xenopus eggs that reach the swimming larval stage (with functional muscle and nerve) goes down from 35% with donor cells at the gastrula stage to 1.7% from tadpole intestinal epithelial cells, a decrease of up to 20 times [15]. In mice, the success of nuclear transfers from ES cells compared to those from adult fibroblasts decreases by 10-fold from 10–20% to approximately 1–2%, scored as the percent of total nuclear transfers that reach birth, as reviewed in [16] (Figure 2b), (but also see [17]). A similar decrease in success rate is seen with nuclear transfers to Xenopus oocytes (first meiotic prophase), when judged by pluripotency gene activation from transplanted nuclei. For example, the absolute number of Sox2 pluripotency gene transcripts synthesised per transplanted nucleus per day goes from 7200 for differentiated