SYSSTEMCELL

Regulatory transcriptional networks orchestrating mouse pluripotent embryonic stem cells

 Coordinatore STICHTING KATHOLIEKE UNIVERSITEIT 

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 Nazionalità Coordinatore Netherlands [NL]
 Totale costo 2˙500˙000 €
 EC contributo 2˙500˙000 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2013-ADG
 Funding Scheme ERC-AG
 Anno di inizio 2014
 Periodo (anno-mese-giorno) 2014-03-01   -   2019-02-28

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    STICHTING KATHOLIEKE UNIVERSITEIT

 Organization address address: GEERT GROOTEPLEIN NOORD 9
city: NIJMEGEN
postcode: 6525 EZ

contact info
Titolo: Mr.
Nome: Geurt
Cognome: Van Renselaar
Email: send email
Telefono: 31243652787
Fax: 31243652787

NL (NIJMEGEN) hostInstitution 2˙500˙000.00
2    STICHTING KATHOLIEKE UNIVERSITEIT

 Organization address address: GEERT GROOTEPLEIN NOORD 9
city: NIJMEGEN
postcode: 6525 EZ

contact info
Titolo: Prof.
Nome: Hendrik Gerard
Cognome: Stunnenberg
Email: send email
Telefono: +31 24 3615157
Fax: +3124 3610520

NL (NIJMEGEN) hostInstitution 2˙500˙000.00

Mappa


 Word cloud

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model    lif    cells    principles    tf    esc    serum    dynamics    expression    post    chromatin    transcription    implantation    distinct    regulation    gene    modules    embryonic    pre    reflect    cell    escs    pluripotent    mouse   

 Obiettivo del progetto (Objective)

'The lack of a quantitative framework around the dynamics of gene expression and its determinants represents a major hurdle for capturing transcription regulation into regulatory models. Embryonic Stem Cells (ESC) provide an excellent cellular model to quantitatively define the principles of gene regulation at the biochemical and (epi)genetic level. In SysStemCell, I will focus on two distinct mouse pluripotent cell states. My recent studies have shown that the epigenome and transcriptome of ESCs maintained in serum-free medium complemented with two kinase inhibitors and LIF (‘2i ESC’) are distinct from classical ESCs cultured in the presence of serum and LIF (‘serum ESC’). Importantly, the 2i ESCs reflect pre-implantation stage ICM cells whereas the widely studied serum cells reflect post-implantation ESCs. These two distinct pluripotent states are interconvertible in vitro, providing an unique and accessible model to explore the regulation of the pre- to post-implantation phase of early embryonic development. I will combine state-of-the-art proteomics and chromatin-based methods, including a novel in vivo UV femtosecond laser crosslinking approach, and in depths bioinformatics in an iterative manner to define the full compendium of transcription (co)factors (TF) and TF-modules that define the two cell states. The dynamics of long- and short-range interactions between these modules will be assessed and correlated with the epigenetic state and chromatin structure. Novel and existing factors will be assessed for their role in differentiation from 2i to serum and reverse programming using knockout and forced expression strategies. Collectively, my studies will provide an invaluable resource for the community and a deep insight in the mechanisms and general principles that orchestrate gene expression in particular in the hitherto unexplored transition at implantation during early mouse development.'

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