RRC ID 54170
Author Hirose M, Hada M, Kamimura S, Matoba S, Honda A, Motomura K, Ogonuki N, Shawki HH, Inoue K, Takahashi S, Ogura A.
Title Aberrant imprinting in mouse trophoblast stem cells established from somatic cell nuclear transfer-derived embryos.
Journal Epigenetics
Abstract Although phenotypic abnormalities frequently appear in the placenta following somatic cell nuclear transfer (SCNT), mouse trophoblast stem cells (TSCs) established from SCNT embryos reportedly show no distinct abnormalities compared with those derived from normal fertilization. In this study, we reexamined SCNT-TSCs to identify their imprinting statuses. Placenta-specific maternally imprinted genes (Gab1, Slc38a4, and Sfmbt2) consistently showed biallelic expression in SCNT-TSCs, suggesting their loss of imprinting (LOI). The LOI of Gab1 was associated with decreased DNA methylation, and that of Sfmbt2 was associated with decreased DNA methylation and histone H3K27 trimethylation. The maternal allele of the intergenic differentially methylated region (IG-DMR) was aberrantly hypermethylated following SCNT, even though this region was prone to demethylation in TSCs when established in a serum-free chemically defined medium. These findings indicate that the development of cloned embryos is associated with imprinting abnormalities specifically in the trophoblast lineage from its initial stage, which may affect subsequent placental development.
Volume 13(7)
Pages 693-703
Published 2018-8-23
DOI 10.1080/15592294.2018.1507199
PMID 30079806
PMC PMC6224209
MeSH Adaptor Proteins, Signal Transducing Amino Acid Transport System A / genetics Amino Acid Transport System A / metabolism Animals Blastocyst / metabolism Blastocyst / pathology Cloning, Organism DNA Methylation Embryonic Stem Cells / metabolism Embryonic Stem Cells / pathology* Epigenesis, Genetic* Female Genomic Imprinting* Mice Mice, Inbred C57BL Nuclear Transfer Techniques / adverse effects* Phosphoproteins / genetics Phosphoproteins / metabolism Placenta / abnormalities* Placenta / metabolism Placenta / pathology Placentation Pregnancy Repressor Proteins Transcription Factors / genetics Transcription Factors / metabolism Trophoblasts / metabolism Trophoblasts / pathology*
IF 4.918
Times Cited 6
Mice RBRC00639