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Mitochondrial Replacement Therapy Embryos Appear Largely Normal in Single-Cell 'Omics Analyses

In PLOS Biology, researchers at Peking University, the Chinese PLA General Hospital, and other centers share findings from a single-cell study centered on blastocyst stage human embryos developed with the help of spindle transfer-based methods for separating nuclear DNA inheritance from the inheritance of mutated maternal mitochondrial DNA. Using a combination of single-cell copy number variant, transcriptome, and DNA methylation profiling methods on nearly 1,400 individual cells, the team compared 46 ST and control blastocysts. While they saw similar gene expression and aneuploidy patterns in both groups of embryos, the authors note that the ST blastocysts appeared to have somewhat delayed trophectoderm tissue DNA demethylation relative to the blastocysts formed without the ST process. "Uncoupling of the inheritance of mtDNA and the nuclear genome by spindle transfer (ST) can potentially prevent the transmission of mtDNA mutations from mother to offspring," they explain, noting that the findings so far "suggest that ST seems generally safe for embryonic development, with a relatively minor delay in the DNA demethylation process at the blastocyst stage."