Reshaping the transcriptional frontier: epigenetics and somatic cell nuclear transfer.

Reshaping the transcriptional frontier: epigenetics and somatic cell nuclear transfer.
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DOI:
10.1002/mrd.22271
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发表时间:
2014-02
影响因子:
2.5
通讯作者:
Golding, Michael C.
Golding, Michael C.
中科院分区:
生物学3区
文献类型:
--
作者:
Long, Charles R.;Westhusin, Mark E.;Golding, Michael C.

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体细胞核移植(SCNT)实验为细胞重编程领域铺平了道路。到目前为止,克隆20多个不同物种的能力已经证明,这项技术很强大,但效率非常低,而且容易出现发育异常。然而,克隆动物的后代没有表现出父母的异常,这表明低效率和高发育死亡率源于表观遗传。将体细胞重新编程为能够发育成可存活后代的全能胚胎的表观遗传障碍是显著的,而且是多种多样的。尽管它们之间关系密切,但在核移植后,染色质结构和转录往往并不统一地重新编程,许多克隆胚胎形成了供体细胞和胚胎卵裂球之间的杂交基因表达谱。细胞重编程的最新进展表明,供体细胞染色质结构向正常胚胎的改变实际上是SCNT胚胎成功发育的限速步骤。在这里,我们回顾了体细胞核转化为能够完全发育的胚胎的相关文献。有趣的是,尽管重置体细胞转录和相关的表观遗传标记对于SCNT胚胎的发育是绝对必要的,但生命并不要求完美。
Somatic-cell nuclear transfer (SCNT) experiments have paved the way to the field of cellular reprogramming. The demonstrated ability to clone over 20 different species to date has proven that the technology is robust but very inefficient, and is prone to developmental anomalies. Yet, the offspring from cloned animals exhibit none of the abnormalities of their parents, suggesting the low efficiency and high developmental mortality are epigenetic in origin. The epigenetic barriers to reprogramming somatic cells into a totipotent embryo capable of developing into a viable offspring are significant and varied. Despite their intimate relationship, chromatin structure and transcription are often not uniformly reprogramed after nuclear transfer, and many cloned embryos develop gene expression profiles that are hybrids between the donor cell and an embryonic blastomere. Recent advances in cellular reprogramming suggest that alteration of donor-cell chromatin structure towards that found in an normal embryo is actually the rate-limiting step in successful development of SCNT embryos. Here we review the literature relevant to the transformation of a somatic-cell nucleus into an embryo capable of full-term development. Interestingly, while resetting somatic transcription and associated epigenetic marks are absolutely required for development of SCNT embryos, life does not demand perfection.
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