RRC ID 27916
Author Hirasawa R, Matoba S, Inoue K, Ogura A.
Title Somatic donor cell type correlates with embryonic, but not extra-embryonic, gene expression in postimplantation cloned embryos.
Journal PLoS One
Abstract The great majority of embryos generated by somatic cell nuclear transfer (SCNT) display defined abnormal phenotypes after implantation, such as an increased likelihood of death and abnormal placentation. To gain better insight into the underlying mechanisms, we analyzed genome-wide gene expression profiles of day 6.5 postimplantation mouse embryos cloned from three different cell types (cumulus cells, neonatal Sertoli cells and fibroblasts). The embryos retrieved from the uteri were separated into embryonic (epiblast) and extraembryonic (extraembryonic ectoderm and ectoplacental cone) tissues and were subjected to gene microarray analysis. Genotype- and sex-matched embryos produced by in vitro fertilization were used as controls. Principal component analysis revealed that whereas the gene expression patterns in the embryonic tissues varied according to the donor cell type, those in extraembryonic tissues were relatively consistent across all groups. Within each group, the embryonic tissues had more differentially expressed genes (DEGs) (>2-fold vs. controls) than did the extraembryonic tissues (P<1.0 × 10(-26)). In the embryonic tissues, one of the common abnormalities was upregulation of Dlk1, a paternally imprinted gene. This might be a potential cause of the occasional placenta-only conceptuses seen in SCNT-generated mouse embryos (1-5% per embryos transferred in our laboratory), because dysregulation of the same gene is known to cause developmental failure of embryos derived from induced pluripotent stem cells. There were also some DEGs in the extraembryonic tissues, which might explain the poor development of SCNT-derived placentas at early stages. These findings suggest that SCNT affects the embryonic and extraembryonic development differentially and might cause further deterioration in the embryonic lineage in a donor cell-specific manner. This could explain donor cell-dependent variations in cloning efficiency using SCNT.
Volume 8(10)
Pages e76422
Published 2013-1-1
DOI 10.1371/journal.pone.0076422
PII PONE-D-13-13369
PMID 24146866
PMC PMC3797840
MeSH Animals Biomarkers / metabolism Calcium-Binding Proteins Cell Separation Cloning, Organism* Embryo Implantation / genetics* Extraembryonic Membranes / metabolism* Female Fertilization in Vitro Gene Expression Profiling Gene Expression Regulation, Developmental* Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism Mice Nuclear Transfer Techniques Oligonucleotide Array Sequence Analysis Principal Component Analysis Reproducibility of Results Tissue Donors Up-Regulation / genetics
IF 2.74
Times Cited 14
Mice RBRC01260