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CellKarma SIGNED

Dissecting the regulatory logic of cell fate reprogramming through integrative and single cell genomics

Total Cost €

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EC-Contrib. €

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Partnership

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 CellKarma project word cloud

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

regenerative    combines    determinants    regulators    ipscs    never    significantly    multifaceted    modulators    cocktail    ultimate    pluripotency    responsible    reprogramming    otherwise    cutting    limited    human    shaping    unlock    isolate    derivation    editing    cellular    pluripotent    revolutionized    intermediates    discovery    expose    successfully    stem    lineage    logic    summary    stimulated    transcription    relationships    events    chance    explore    acquire    decisions    single    vitro    reconstruct    strategies    biology    patient    primary    genome    light    dissect    mutagenesis    developmental    right    pressing    transitions    directions    regions    synthetic    utilize    medicine    multiple    therapies    genomic    modulate    edge    unidentified    alternative    transcriptomics    barriers    integrative    identity    cell    quality    transcriptional    ipsc    cells    rules    fate    full    technologies    molecular    conversion    regulatory    enhancer    promoters    driving   

Project "CellKarma" data sheet

The following table provides information about the project.

Coordinator
FONDAZIONE TELETHON 

Organization address
address: VIA VARESE 16/B
city: ROMA
postcode: 185
website: www.telethon.it

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 Italy [IT]
 Total cost 1˙497˙250 €
 EC max contribution 1˙497˙250 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-STG
 Funding Scheme ERC-STG
 Starting year 2018
 Duration (year-month-day) from 2018-03-01   to  2023-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FONDAZIONE TELETHON IT (ROMA) coordinator 1˙497˙250.00

Map

 Project objective

The concept that any cell type, upon delivery of the right “cocktail” of transcription factors, can acquire an identity that otherwise it would never achieve, revolutionized the way we approach the study of developmental biology. In light of this, the discovery of induced pluripotent stem cells (IPSCs) and cell fate conversion approaches stimulated new research directions into human regenerative biology. However, the chance to successfully develop patient-tailored therapies is still very limited because reprogramming technologies are applied without a comprehensive understanding of the molecular processes involved. Here, I propose a multifaceted approach that combines a wide range of cutting-edge integrative genomic strategies to significantly advance our understanding of the regulatory logic driving cell fate decisions during human reprogramming to pluripotency. To this end, I will utilize single cell transcriptomics to isolate reprogramming intermediates, reconstruct their lineage relationships and define transcriptional regulators responsible for the observed transitions (AIM 1). Then, I will dissect the rules by which transcription factors modulate the activity of promoters and enhancer regions during reprogramming transitions, by applying synthetic biology and genome editing approaches (AIM 2). Then, I will adopt an alternative approach to identify reprogramming modulators by the analysis of reprogramming-induced mutagenesis events (AIM 3). Finally, I will explore my findings in multiple primary reprogramming approaches to pluripotency, with the ultimate goal of improving the quality of IPSC derivation (Aim 4). In summary, this project will expose novel determinants and yet unidentified molecular barriers of reprogramming to pluripotency and will be essential to unlock the full potential of reprogramming technologies for shaping cellular identity in vitro and to address pressing challenges of regenerative medicine.

 Publications

year authors and title journal last update
List of publications.
2018 Davide Cacchiarelli, Xiaojie Qiu, Sanjay Srivatsan, Anna Manfredi, Michael Ziller, Eliah Overbey, Antonio Grimaldi, Jonna Grimsby, Prapti Pokharel, Kenneth J. Livak, Shuqiang Li, Alexander Meissner, Tarjei S. Mikkelsen, John L. Rinn, Cole Trapnell
Aligning Single-Cell Developmental and Reprogramming Trajectories Identifies Molecular Determinants of Myogenic Reprogramming Outcome
published pages: 258-268.e3, ISSN: 2405-4712, DOI: 10.1016/j.cels.2018.07.006
Cell Systems 7/3 2019-11-07
2018 Marcella Cesana, Michael H. Guo, Davide Cacchiarelli, Lara Wahlster, Jessica Barragan, Sergei Doulatov, Linda T. Vo, Beatrice Salvatori, Cole Trapnell, Kendell Clement, Patrick Cahan, Kaloyan M. Tsanov, Patricia M. Sousa, Barbara Tazon-Vega, Adriano Bolondi, Federico M. Giorgi, Andrea Califano, John L. Rinn, Alexander Meissner, Joel N. Hirschhorn, George Q. Daley
A CLK3-HMGA2 Alternative Splicing Axis Impacts Human Hematopoietic Stem Cell Molecular Identity throughout Development
published pages: 575-588.e7, ISSN: 1934-5909, DOI: 10.1016/j.stem.2018.03.012
Cell Stem Cell 22/4 2019-11-07

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