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ReachingCompleteness SIGNED

The Molecular Basis of Somatic Nuclear Reprogramming

Total Cost €

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EC-Contrib. €

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Partnership

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 ReachingCompleteness project word cloud

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leads    transcriptome    stringent    pluripotent    majority    signal    exhibit    dictate    edge    grant    ipscs    establishing    trace    cutting    pluripotency    crispr    hurdles    reprogramming    global    molecular    incomplete    molecule    therapy    measured    mechanisms    degree    safe    cells    quality    cas9    overview    screening    direct    complete    patient    successful    biomark    poor    tests    knock    basic    drug    nuclear    seq    hinder    technologies    bioinformatic    rare    overcome    parallel    types    stable    efforts    transcriptional    sophisticated    single    critical    solely    aberrant    suggests    generation    vast    somatic    deciphering    conversion    employing    invaluable    converted    uncover    uncovering    detect    stem    reporter    mrna    tools    segregate    disease    capture    rna    models    prevailing    ideal    developmental    reprogrammable    profile    monitor    infancy    resource    cell    intend    noise    fluorescent    fluidigm    limitations    progress    fish    ratio   

Project "ReachingCompleteness" data sheet

The following table provides information about the project.

Coordinator
THE HEBREW UNIVERSITY OF JERUSALEM 

Organization address
address: EDMOND J SAFRA CAMPUS GIVAT RAM
city: JERUSALEM
postcode: 91904
website: www.huji.ac.il

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 Israel [IL]
 Project website http://www.buganimlab.com
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-03-01   to  2021-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE HEBREW UNIVERSITY OF JERUSALEM IL (JERUSALEM) coordinator 1˙500˙000.00

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 Project objective

The direct conversion approach and the generation of induced pluripotent stem cells (iPSCs) provide an invaluable resource of cells for disease modelling, drug screening, and patient-specific cell-based therapy. However, the directly converted cells are not stable, and the vast majority of iPSCs exhibit poor developmental potential as measured by stringent pluripotency tests. This suggests that the prevailing method of reprogramming is not ideal and leads to aberrant/incomplete conversion. To improve the quality of the converted cells, efforts should be focused on uncovering the molecular mechanisms that characterize the nuclear reprogramming process. There are two critical hurdles that hinder the progress of deciphering the elements that dictate successful reprogramming: (1) The ability to detect and capture solely the rare cells that eventually will be converted and (2) to monitor the transcriptional profile of cells at the single-cell level. Single-cell technology is in its infancy and many of the methods used today are characterized by high noise to signal ratio. In this grant proposal we intend to overcome these limitations by (1) establishing a complex fluorescent knock-in reporter system using the CRISPR/Cas9 method to capture the early rare reprogrammable cells and by (2) employing several cutting-edge single-cell technologies, RNA-Seq, Fluidigm BioMark and single-molecule mRNA-FISH, to segregate the real signal from the noise. To identify common and more global elements that facilitate nuclear reprogramming at large, we will trace in parallel, reprogrammable cells from two different somatic cell conversion models that reach high degree of nuclear reprogramming, and analyse their transcriptome using sophisticated bioinformatic tools. This study will provide a general overview of the changes that occur during the conversion of various cell types and will uncover the basic features that are essential to reach safe and complete conversion.

 Publications

year authors and title journal last update
List of publications.
2017 Mohammad Jaber, Shulamit Sebban, Yosef Buganim
Acquisition of the pluripotent and trophectoderm states in the embryo and during somatic nuclear reprogramming
published pages: 37-43, ISSN: 0959-437X, DOI: 10.1016/j.gde.2017.06.012
Current Opinion in Genetics & Development 46 2019-07-08

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