Coexpression analysis identifies nuclear reprogramming barriers of somatic cell nuclear transfer embryos

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.

[1]  Yan Jiang,et al.  Interspecies Somatic Cell Nuclear Transfer Is Dependent on Compatible Mitochondrial DNA and Reprogramming Factors , 2011, PloS one.

[2]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[3]  K. Rudolph,et al.  Enhanced telomere rejuvenation in pluripotent cells reprogrammed via nuclear transfer relative to induced pluripotent stem cells. , 2014, Cell stem cell.

[4]  M. DePamphilis,et al.  A unique role for enhancers is revealed during early mouse development , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[5]  K. Miyamoto,et al.  Nuclear reprogramming of sperm and somatic nuclei in eggs and oocytes , 2013, Reproductive medicine and biology.

[6]  Miler T. Lee,et al.  Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition , 2013, Nature.

[7]  E. Memili,et al.  Reprogramming mammalian somatic cells. , 2012, Theriogenology.

[8]  Yongyan Wu,et al.  Identification of differentially expressed microRNAs in placentas of cloned and normally produced calves by Solexa sequencing. , 2015, Animal reproduction science.

[9]  H. Otu,et al.  Reprogrammed Transcriptome in Rhesus-Bovine Interspecies Somatic Cell Nuclear Transfer Embryos , 2011, PloS one.

[10]  Li Li,et al.  Gene co‐expression analysis identifies common modules related to prognosis and drug resistance in cancer cell lines , 2014, International journal of cancer.

[11]  D. Amarnath,et al.  Nuclear-cytoplasmic incompatibility and inefficient development of pig-mouse cytoplasmic hybrid embryos. , 2011, Reproduction.

[12]  Matthew D. Schultz,et al.  Abnormalities in human pluripotent cells due to reprogramming mechanisms , 2014, Nature.

[13]  H. Niemann Epigenetic reprogramming in mammalian species after SCNT-based cloning. , 2016, Theriogenology.

[14]  S. Mitalipov,et al.  Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer , 2013, Cell.

[15]  Dong Ryul Lee,et al.  Human somatic cell nuclear transfer using adult cells. , 2014, Cell stem cell.

[16]  Kimiko Inoue,et al.  Recent advancements in cloning by somatic cell nuclear transfer , 2013, Philosophical Transactions of the Royal Society B: Biological Sciences.

[17]  L. Laurent,et al.  Incompatibility between Nuclear and Mitochondrial Genomes Contributes to an Interspecies Reproductive Barrier. , 2016, Cell metabolism.

[18]  Jun Liu,et al.  Genome-wide analysis of DNA methylation in bovine placentas , 2014, BMC Genomics.

[19]  S. Antonini,et al.  Development, embryonic genome activity and mitochondrial characteristics of bovine-pig inter-family nuclear transfer embryos. , 2010, Reproduction.

[20]  Giovanna Lazzari,et al.  Interspecies somatic cell nuclear transfer: advancements and problems. , 2013, Cellular reprogramming.

[21]  Zekun Guo,et al.  Expression and methylation status of imprinted genes in placentas of deceased and live cloned transgenic calves. , 2011, Theriogenology.

[22]  E. Wolf,et al.  Formation of nucleoli in interspecies nuclear transfer embryos derived from bovine, porcine, and rabbit oocytes and nuclear donor cells of various species. , 2011, Reproduction.

[23]  Yong Zhang,et al.  Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos , 2016, Nature.

[24]  M. Araúzo-Bravo,et al.  Somatic cell nuclear reprogramming of mouse oocytes endures beyond reproductive decline , 2011, Aging cell.

[25]  B. Barboni,et al.  Genetic rescue of an endangered mammal by cross-species nuclear transfer using post-mortem somatic cells , 2001, Nature Biotechnology.

[26]  Yongyan Wu,et al.  Aberrant mRNA expression and DNA methylation levels of imprinted genes in cloned transgenic calves that died of large offspring syndrome , 2011 .

[27]  Md. Munir Hossain,et al.  Massive deregulation of miRNAs from nuclear reprogramming errors during trophoblast differentiation for placentogenesis in cloned pregnancy , 2014, BMC Genomics.

[28]  Steve Horvath,et al.  WGCNA: an R package for weighted correlation network analysis , 2008, BMC Bioinformatics.

[29]  I. Choi,et al.  Somatic cell nuclear transfer: Past, present and future perspectives. , 2007, Theriogenology.

[30]  P. Ross,et al.  Bovine ooplasm partially remodels primate somatic nuclei following somatic cell nuclear transfer. , 2009, Cloning and stem cells.

[31]  M. Stoneking,et al.  Evaluating intra- and inter-individual variation in the human placental transcriptome , 2014, bioRxiv.

[32]  A. Ogura,et al.  A New, Dynamic Era for Somatic Cell Nuclear Transfer? , 2016, Trends in biotechnology.

[33]  P. Loi,et al.  Interspecies somatic cell nuclear transfer: a salvage tool seeking first aid. , 2011, Theriogenology.

[34]  Mingzhi Liao,et al.  Exploring timing activation of functional pathway based on differential co-expression analysis in preimplantation embryogenesis , 2016, Oncotarget.

[35]  G. Pan,et al.  Somatic cell reprogramming for regenerative medicine: SCNT vs. iPS cells , 2012, BioEssays : news and reviews in molecular, cellular and developmental biology.

[36]  S. Horvath,et al.  Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing , 2013, Nature.

[37]  Ashley R Bonneau,et al.  Zygotic genome activation during the maternal-to-zygotic transition. , 2014, Annual review of cell and developmental biology.

[38]  E. Wolf,et al.  Fine mapping of genome activation in bovine embryos by RNA sequencing , 2014, Proceedings of the National Academy of Sciences.

[39]  Juan Carlos Izpisua Belmonte,et al.  Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development , 2011, Development.

[40]  H. Lewin,et al.  Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning , 2007, Nature Genetics.

[41]  Shogo Matoba,et al.  Embryonic Development following Somatic Cell Nuclear Transfer Impeded by Persisting Histone Methylation , 2014, Cell.

[42]  Chunling Bai,et al.  Irregular transcriptome reprogramming probably causes thec developmental failure of embryos produced by interspecies somatic cell nuclear transfer between the Przewalski’s gazelle and the bovine , 2014, BMC Genomics.