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

Ábel Vértesy, Wibowo Arindrarto, Matthias S Roost, Björn Reinius, Vanessa Torrens-Juaneda, Monika Bialecka, Ioannis Moustakas, Yavuz Ariyurek, Ewart Kuijk, Hailiang Mei, Rickard Sandberg, Alexander van Oudenaarden, Susana M Chuva de Sousa Lopes

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1873
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 14 May 2018

Keywords

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

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