Single-cell multiomics analyses of spindle-transferred human embryos suggest a mostly normal embryonic development

PLoS Biol. 2022 Aug 16;20(8):e3001741. doi: 10.1371/journal.pbio.3001741. eCollection 2022 Aug.


Mitochondrial DNA (mtDNA) mutations are often associated with incurable diseases and lead to detectable pathogenic variants in 1 out of 200 babies. 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. However, no well-established studies have critically assessed the safety of this technique. Here, using single-cell triple omics sequencing method, we systematically analyzed the genome (copy number variation), DNA methylome, and transcriptome of ST and control blastocysts. The results showed that, compared to that in control embryos, the percentage of aneuploid cells in ST embryos did not significantly change. The epiblast, primitive endoderm, and trophectoderm (TE) of ST blastocysts presented RNA expression profiles that were comparable to those of control blastocysts. However, the DNA demethylation process in TE cells of ST blastocysts was slightly slower than that in the control blastocysts. Collectively, our results suggest that ST seems generally safe for embryonic development, with a relatively minor delay in the DNA demethylation process at the blastocyst stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Blastocyst* / metabolism
  • DNA Copy Number Variations*
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Embryonic Development / genetics
  • Female
  • Humans
  • Pregnancy


  • DNA, Mitochondrial

Grants and funding

This work was supported by grants from the National Key R&D Program of China (2018YFA0107601) (to FT) and the National Key R&D Program of China (2018YFC1003003) (to WS) ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.