Parental haplotype-specific single-cell transcriptomics reveal incomplete epigenetic reprogramming in human female germ cells

Nat Commun. 2018 May 14;9(1):1873. doi: 10.1038/s41467-018-04215-7.


In contrast to mouse, human female germ cells develop asynchronously. Germ cells transition to meiosis, erase genomic imprints, and reactivate the X chromosome. It is unknown if these events all appear asynchronously, and how they relate to each other. Here we combine exome sequencing of human fetal and maternal tissues with single-cell RNA-sequencing of five donors. We reconstruct full parental haplotypes and quantify changes in parental allele-specific expression, genome-wide. First we distinguish primordial germ cells (PGC), pre-meiotic, and meiotic transcriptional stages. Next we demonstrate that germ cells from various stages monoallelically express imprinted genes and confirm this by methylation patterns. Finally, we show that roughly 30% of the PGCs are still reactivating their inactive X chromosome and that this is related to transcriptional stage rather than fetal age. Altogether, we uncover the complexity and cell-to-cell heterogeneity of transcriptional and epigenetic remodeling in female human germ cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Legal
  • Adult
  • Chromosomes, Human, X / chemistry*
  • Chromosomes, Human, X / metabolism
  • DNA Methylation
  • Epigenesis, Genetic*
  • Exome Sequencing
  • Female
  • Fetus
  • Genetic Heterogeneity
  • Genomic Imprinting
  • Haplotypes
  • Humans
  • Male
  • Meiosis
  • Ovum / growth & development
  • Ovum / metabolism*
  • Pregnancy
  • Pregnancy Trimesters
  • Single-Cell Analysis / methods
  • Transcriptome*
  • X Chromosome Inactivation