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XPGCS SIGNED

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

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

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.

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

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 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.	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

List of publications.
year	authors and title	journal	last update
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, LaurÃ¨ne 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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