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

doi:10.1038/s41467-018-04215-7

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

44 Citations (Scopus)

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 language	English
Pages (from-to)	1873
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04215-7
Publication status	Published - 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

Access to Document

10.1038/s41467-018-04215-7

Cite this

Vértesy, Á., Arindrarto, W., Roost, M. S., Reinius, B., Torrens-Juaneda, V., Bialecka, M., Moustakas, I., Ariyurek, Y., Kuijk, E., Mei, H., Sandberg, R., van Oudenaarden, A., & Chuva de Sousa Lopes, S. M. (2018). Parental haplotype-specific single-cell transcriptomics reveal incomplete epigenetic reprogramming in human female germ cells. Nature Communications, 9(1), 1873. https://doi.org/10.1038/s41467-018-04215-7

@article{bc498e96b01246ca8a7599e304b59a94,

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

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.",

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",

author = "{\'A}bel V{\'e}rtesy and Wibowo Arindrarto and Roost, {Matthias S} and Bj{\"o}rn Reinius and Vanessa Torrens-Juaneda and Monika Bialecka and Ioannis Moustakas and Yavuz Ariyurek and Ewart Kuijk and Hailiang Mei and Rickard Sandberg and {van Oudenaarden}, Alexander and {Chuva de Sousa Lopes}, {Susana M}",

year = "2018",

month = may,

day = "14",

doi = "10.1038/s41467-018-04215-7",

language = "English",

volume = "9",

pages = "1873",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Vértesy, Á, Arindrarto, W, Roost, MS, Reinius, B, Torrens-Juaneda, V, Bialecka, M, Moustakas, I, Ariyurek, Y, Kuijk, E, Mei, H, Sandberg, R, van Oudenaarden, A & Chuva de Sousa Lopes, SM 2018, 'Parental haplotype-specific single-cell transcriptomics reveal incomplete epigenetic reprogramming in human female germ cells', Nature Communications, vol. 9, no. 1, pp. 1873. https://doi.org/10.1038/s41467-018-04215-7

TY - JOUR

T1 - Parental haplotype-specific single-cell transcriptomics reveal incomplete epigenetic reprogramming in human female germ cells

AU - Vértesy, Ábel

AU - Arindrarto, Wibowo

AU - Roost, Matthias S

AU - Reinius, Björn

AU - Torrens-Juaneda, Vanessa

AU - Bialecka, Monika

AU - Moustakas, Ioannis

AU - Ariyurek, Yavuz

AU - Kuijk, Ewart

AU - Mei, Hailiang

AU - Sandberg, Rickard

AU - van Oudenaarden, Alexander

AU - Chuva de Sousa Lopes, Susana M

PY - 2018/5/14

Y1 - 2018/5/14

N2 - 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.

AB - 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.

KW - Abortion, Legal

KW - Adult

KW - Chromosomes, Human, X/chemistry

KW - DNA Methylation

KW - Epigenesis, Genetic

KW - Female

KW - Fetus

KW - Genetic Heterogeneity

KW - Genomic Imprinting

KW - Haplotypes

KW - Humans

KW - Male

KW - Meiosis

KW - Ovum/growth & development

KW - Pregnancy

KW - Pregnancy Trimesters

KW - Single-Cell Analysis/methods

KW - Transcriptome

KW - Whole Exome Sequencing

KW - X Chromosome Inactivation

U2 - 10.1038/s41467-018-04215-7

DO - 10.1038/s41467-018-04215-7

M3 - Article

C2 - 29760424

SN - 2041-1723

VL - 9

SP - 1873

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this