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XPGCS SIGNED

Single cell profiling of X chromosome reactivation during primordial germ cell specification in vivo

Total Cost €

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EC-Contrib. €

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Partnership

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 XPGCS project word cloud

Explore the words cloud of the XPGCS project. It provides you a very rough idea of what is the project "XPGCS" about.

innovative    altogether    extensive    sequence    embryos    generations    mice    coating    entire    precursors    enrichment    conjunction    conditional    mutant    kinetics    genomic    imprints    single    inactivated    dosage    progressive    biallelic    demethylase    explore    transmit    cells    gene    chromosomes    mapped    transcriptome    xci    linked    reprogramming    plays    subsequent    histone    genes    regulation    monitoring    undergoes    xp    specification    unravel    model    global    reactivation    xist    maternal    expression    utx    insights    c57bl    genetic    castaneus    xm    genders    primordial    initiation    eggs    compensation    xi    repressive    erasure    coding    female    perform    pgcs    epigenetic    f1    mechanisms    mark    dynamics    inactivation    h3k27me3    followed    paternal    mouse    hybrid    multidisciplinary    chromosome    cell    rate    polymorphisms    sperm    roles    parallel    methylation    germline    pgc    inactive    germ    provides    little    chromatin    rna    strains    allele   

Project "XPGCS" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE 

Organization address
address: TRINITY LANE THE OLD SCHOOLS
city: CAMBRIDGE
postcode: CB2 1TN
website: www.cam.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website https://www.gurdon.cam.ac.uk/research/surani
 Total cost 195˙454 €
 EC max contribution 195˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-03-01   to  2018-04-17

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE UK (CAMBRIDGE) coordinator 195˙454.00

Map

 Project objective

In female mice, one of the two X chromosomes is inactivated during early development to ensure dosage compensation between genders. A long non-coding gene, Xist, plays a crucial role in the initiation of the X chromosome inactivation (XCI) process. Primordial germ cells (PGCs), the precursors of sperm and eggs, transmit genetic and epigenetic information to subsequent generations, following extensive reprogramming, erasure of methylation and genomic imprints, and X chromosome reactivation. The inactive X (Xi) then undergoes progressive reprogramming and reactivation in the germline of female embryos, through the loss of Xist RNA coating, followed by the erasure of the repressive H3K27me3 histone mark, and eventually biallelic expression of X-linked genes. Although the global dynamics of Xi reactivation have been mapped little is known about the gene-specific dynamics, or the mechanisms involved. To explore gene activity on the entire X chromosome during reprogramming in the germline, I will perform single-cell transcriptome analyses on PGCs from C57BL/6 X Castaneus F1 female hybrid embryos. The high rate of sequence polymorphisms between these strains provides allele-specific information for the activity of the Xp (paternal X) and the Xm (maternal X). I will investigate the kinetics of Xp and Xm gene reactivation chromosome-wide at the single cell level following PGC specification. Furthermore, I will study the dynamics of the expression of X-linked genes in conjunction with chromatin changes in PGCs by monitoring the loss of H3K27me3 enrichment on the inactive X chromosome. In parallel, I will study how the regulation of H3K27me3 affect Xi reactivation by using a conditional mutant mouse model of a H3K27me3 demethylase, UTX. Altogether, the innovative and multidisciplinary approach of this study will unravel important insights on germline reprogramming and the roles of chromatin changes associated with X chromosome reactivation.

 Publications

year authors and title journal last update
List of publications.
2018 Jan J Zylicz, Maud Borensztein, Frederick CK Wong, Yun Huang, Caroline Lee, Sabine Dietmann, M Azim Surani
G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.33361
eLife 7 2019-06-13
2017 Maud Borensztein, Ikuhiro Okamoto, Laurène Syx, Guillaume Guilbaud, Christel Picard, Katia Ancelin, Rafael Galupa, Patricia Diabangouaya, Nicolas Servant, Emmanuel Barillot, Azim Surani, Mitinori Saitou, Chong-Jian Chen, Konstantinos Anastassiadis, Edith Heard
Contribution of epigenetic landscapes and transcription factors to X-chromosome reactivation in the inner cell mass
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-01415-5
Nature Communications 8/1 2019-06-13

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