Uncovering the transcriptional basis of natural cell fate transdifferentiation

• Research unit: COST
• Project number: C15.0076

Key words (English)

Transdifferentiation; Cell Fate; Epigenetics; C. elegans; DamID

Research programs (English)

COST-Action BM1408 - GENiE, A collaborative European network of C. elegans early-stage researchers and young principal investigators

Short description (English)

Over the course of development, cells progressively lose their pluripotency. Originally thought to be definitive, this loss was shown to be reversible and cell identity tunable, sparking great hopes for cellular replacement therapies in regenerative medicine. However, the factors involved in controlling, maintaining or erasing cell identity and their effect on the transcriptional program remain largely unknown. With this project, we propose to characterize how the expression programme is altered during a single cell conversion, and how crucial this is for the reprogramming process, using a robust, natural and genetically tractable transdifferentiation system, the rectal Y to neural PDA conversion in C. elegans. Using genetic screens, this system uncovered a number of nuclear proteins essential for transdifferentiation, but their target genes and more globally the transcriptional output of their action is unknown. This is largely due to the technical difficulty to analyse on the genome-wide level transcription in single transdifferentiating cells from animals. To overcome this roadblock, we propose to map RNA polymerase II binding sites using a highly sensitive genome-wide mapping technique (DamID-seq), coupled to sorting of the nuclei of the transdifferentiating cell. By characterizing the transcriptional basis of transdifferentiation, we hope to uncover the regulatory logic underlying transdifferentiation and use the genetic toolbox of the nematode to characterize the transcriptional function of cell identity regulators during cell fate changes.

Partners and International Organizations (English)

AT; BE; CZ; DK; FI; FR; DE; EL; HU; IL; NL; NO; PL; PT; ES; SE; TR: UK

Abstract (English)

See short description

References in databases (English)

Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. [phone] Swiss Project-Number: C15.0076