Abstract
The success of cloned animal “Dolly Sheep” demonstrated the somatic cell nuclear transfer (SCNT) technique holds huge potentials for mammalian asexual reproduction. However, the extremely poor development of SCNT embryos indicates their molecular mechanism remain largely unexplored. Deciphering the spatiotemporal patterns of gene expression in SCNT embryos is a crucial step toward understanding the mechanisms associated with nuclear reprogramming. In this study, a valuable transcriptome recourse of SCNT embryos was firstly established, which derived from different inter-/intra donor cells. The gene co-expression analysis identified 26 cell-specific modules, and a series of regulatory pathways related to reprogramming barriers were further enriched. Compared to the intra-SCNT embryos, the inter-SCNT embryos underwent only complete partially reprogramming. As master genome trigger genes, the transcripts related to TFIID subunit, RNA polymerase and mediators were incomplete activated in inter-SCNT embryos. The inter-SCNT embryos only wasted the stored maternal mRNA of master regulators, but failed to activate their self-sustained pathway of RNA polymerases. The KDM family of epigenetic regulator also seriously delayed in inter-SCNT embryo reprogramming process. Our study provided new insight into understanding of the mechanisms of nuclear reprogramming.
Highlights
Somatic cell nuclear transfer (SCNT) is a technology to create an exact genetic match of the donor by transferring the donor nucleus into the enucleated recipient oocyte [1]
Total gene expression profiles of somatic cell nuclear transfer (SCNT) embryos derived from different species The inter-SCNT is an ideal method for studying the nuclear-cytoplasmic interactions of cell reprogramming
To identify the earliest transcriptional differences between 8-cell embryos derived through inter-SCNT and intra-SCNT, we performed microarray experiments using pooled embryos (450-500 embryos/samples) at 8-cell stages (Figure 1A)
Summary
Somatic cell nuclear transfer (SCNT) is a technology to create an exact genetic match of the donor by transferring the donor nucleus into the enucleated recipient oocyte [1]. Upon transfer of a www.impactjournals.com/oncotarget somatic nucleus to an enucleated recipient oocyte during the cloning process, several essential changes must ensue [7, 8] In doing so, it must shed its differentiated phenotype and gain a new pluripotent state. It must shed its differentiated phenotype and gain a new pluripotent state All these changes involve a remodeling, not of the underlying genetic sequences that comprise the genome, but of the epigenetic regulator play crucial roles reestablishment of well-orchestrated gene expression [9, 10]. In this process, we believe that there are many barriers in the cell reprogramming process and the underlying molecule mechanisms are poorly unraveled
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