Bioresource Engineering Division, Bioresource Research Center, RIKEN, Tsukuba, Ibaraki, Japan.
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Reproduction. 2021 Jun 11;162(1):F45-F58. doi: 10.1530/REP-21-0013.
Twenty-five years have passed since the birth of Dolly the sheep, the first mammalian clone produced by adult somatic cell nuclear transfer (SCNT). During that time, the main thrust of SCNT-related research has been the elucidation of SCNT-associated epigenetic abnormalities and their correction, with the aim of improving the efficiency of cloned animal production. Through these studies, it has become clear that some epigenomic information can be reprogrammed by the oocyte, while some cannot. Now we know that the imprinting memories in the donor genome, whether canonical (DNA-methylation-dependent) or noncanonical (H3K27me3-dependent), are not reprogrammed by SCNT. Thus, SCNT-derived embryos have the normal canonical imprinting and the erased noncanonical imprinting, both being inherited from the donor cells. The latter can cause abnormal phenotypes in SCNT-derived placentas arising from biallelic expressions of noncanonically imprinted genes. By contrast, repressive epigenomic information, such as DNA methylation and histone modifications, might be more variably reprogrammed, leaving room for technical improvements. Low-input analytical technologies now enable us to analyze the genome of gametes and embryos in a high-throughput, genome-wide manner. These technologies are being applied rapidly to the SCNT field, providing evidence for incomplete reprogramming of the donor genome in cloned embryos or offspring. Insights from the study of epigenetic phenomena in SCNT are highly relevant for our understanding of the mechanisms of genomic reprogramming that can induce totipotency in the mammalian genome.
绵羊多利诞生至今已有 25 年，它是通过成年体细胞核移植（SCNT）技术产生的首例哺乳动物克隆。在此期间，SCNT 相关研究的主要方向是阐明 SCNT 相关的表观遗传异常及其纠正，以提高克隆动物生产的效率。通过这些研究，人们清楚地认识到，卵母细胞可以重编程一些表观基因组信息，而有些则不能。现在我们知道，供体基因组中的印迹记忆，无论是经典的（依赖于 DNA 甲基化）还是非经典的（依赖于 H3K27me3），都不能通过 SCNT 进行重编程。因此，SCNT 衍生的胚胎具有正常的经典印迹和被抹去的非经典印迹，两者均来自供体细胞。后者可能导致源自非经典印迹基因的双等位基因表达的 SCNT 衍生胎盘出现异常表型。相比之下，抑制性表观基因组信息，如 DNA 甲基化和组蛋白修饰，可能会有更多的可变性重编程，为技术改进留出空间。低投入的分析技术现在使我们能够以高通量、全基因组的方式分析配子和胚胎的基因组。这些技术正在迅速应用于 SCNT 领域，为克隆胚胎或后代中供体基因组不完全重编程提供了证据。SCNT 中表观遗传现象的研究结果对于我们理解能够诱导哺乳动物基因组全能性的基因组重编程机制具有重要意义。
