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

Nature Communications
Ábel VértesySusana M Chuva de Sousa Lopes

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.

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Citations

Oct 23, 2019·Molecular Biology and Evolution·Claudius VincenzBeverly I Strassmann
Jul 20, 2019·Nature Communications·X FanS M Chuva de Sousa Lopes
Sep 16, 2020·International Journal of Molecular Sciences·Martin A Estermann, Craig A Smith
Jan 5, 2020·Development·Catherine PatratClaire Rougeulle
Dec 2, 2020·Nature Cell Biology·Jean-François Ouimette, Claire Rougeulle
Mar 17, 2021·Development·Grace V HancockAmander T Clark
May 13, 2021·Stem Cell Reports·Ramiro AlberioM Azim Surani
Sep 10, 2021·Nature·Muzlifah HaniffaUNKNOWN Human Cell Atlas Developmental Biological Network
Oct 1, 2021·Science·Mitinori Saitou, Katsuhiko Hayashi

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Datasets Mentioned

BETA
GSE63818
GSE79280

Methods Mentioned

BETA
exome sequencing
single-cell sequencing
Fluorescence
PCR
chips
Assay
FACS

Software Mentioned

house
Bioconductor
BD Diva
rsem
Bismark
Trim Galore
SortSam
FastQC
gplots
BWA MEM aligner

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