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

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.

Keywords: SCNT embryos; abnormal gene expression; gene regulatory networks; molecular barriers; transcription pathways.

MeSH terms

  • Animals
  • Blastocyst / metabolism
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks*
  • Mice
  • Nuclear Transfer Techniques / adverse effects*
  • RNA-Seq
  • Single-Cell Analysis
  • Transcription, Genetic
  • Transcriptome*