CellKarma SIGNED
Dissecting the regulatory logic of cell fate reprogramming through integrative and single cell genomics
Total Cost €
0EC-Contrib. €
0Partnership
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Project "CellKarma" data sheet
The following table provides information about the project.
| Coordinator |
FONDAZIONE TELETHON
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 1 | FONDAZIONE TELETHON | IT (ROMA) | coordinator | 1˙497˙250.00 |
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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 |
|---|---|---|---|
| 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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