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CellKarma SIGNED

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

Total Cost €

EC-Contrib. €

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.

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

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 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.	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

List of 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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The information about "CELLKARMA" are provided by the European Opendata Portal: CORDIS opendata.