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核移植阻滞胚胎显示转录途径相关基因的广泛失调。

Nuclear Transfer Arrest Embryos Show Massive Dysregulation of Genes Involved in Transcription Pathways.

机构信息

State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot 010020, China.

出版信息

Int J Mol Sci. 2021 Jul 30;22(15):8187. doi: 10.3390/ijms22158187.

Abstract

Somatic cell nuclear transfer (SCNT) technology can reprogram terminally differentiated cell nuclei into a totipotent state. However, the underlying molecular barriers of SCNT embryo development remain incompletely elucidated. Here, we observed that transcription-related pathways were incompletely activated in nuclear transfer arrest (NTA) embryos compared to normal SCNT embryos and in vivo fertilized (WT) embryos, which hinders the development of SCNT embryos. We further revealed the transcription pathway associated gene regulatory networks (GRNs) and found the aberrant transcription pathways can lead to the massive dysregulation of genes in NTA embryos. The predicted target genes of transcription pathways contain a series of crucial factors in WT embryos, which play an important role in catabolic process, pluripotency regulation, epigenetic modification and signal transduction. In NTA embryos, however, these genes were varying degrees of inhibition and show a defect in synergy. Overall, our research found that the incomplete activation of transcription pathways is another potential molecular barrier for SCNT embryos besides the incomplete reprogramming of epigenetic modifications, broadening the understanding of molecular mechanism of SCNT embryonic development.

摘要

体细胞核移植 (SCNT) 技术可以将终末分化的细胞核重编程为全能状态。然而,SCNT 胚胎发育的潜在分子障碍仍不完全清楚。在这里,我们观察到与正常 SCNT 胚胎和体内受精 (WT) 胚胎相比,核转移阻滞 (NTA) 胚胎中的转录相关途径未被完全激活,这阻碍了 SCNT 胚胎的发育。我们进一步揭示了与转录途径相关的基因调控网络 (GRN),并发现异常的转录途径会导致 NTA 胚胎中大量基因的失调。转录途径的预测靶基因包含 WT 胚胎中一系列关键因子,这些因子在代谢过程、多能性调控、表观遗传修饰和信号转导中发挥重要作用。然而,在 NTA 胚胎中,这些基因被不同程度地抑制,并表现出协同作用的缺陷。总的来说,我们的研究发现,除了表观遗传修饰的不完全重编程之外,转录途径的不完全激活是 SCNT 胚胎的另一个潜在分子障碍,拓宽了对 SCNT 胚胎发育分子机制的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee3d/8347363/1f68eac3edf9/ijms-22-08187-g001.jpg

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