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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.

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

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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