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CellKarma

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Dissecting the regulatory logic of cell fate reprogramming through integrative a...

Dissecting the regulatory logic of cell fate reprogramming through integrative and single cell genomics 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. I... ver más

31/08/2024

FONDAZIONE TELETHO...

1M€

Presupuesto del proyecto: 1M€

Líder del proyecto

FONDAZIONE TELETHON ETS No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Ver 2 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2024-08-31

ERC-2017-STG: ERC Starting Grant

I+D

Cerrada hace 8 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

2 Participantes

FONDAZIONE TELETHON ETS

1.50M€ | Lider

HERMANOS PAJUELO

670.66K€ | Participante

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Duración del proyecto: 82 meses Fecha Inicio: 2017-10-06
Fecha Fin: 2024-08-31

Líder del proyecto

FONDAZIONE TELETHON ETS No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 1M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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