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SPLICE-STEM

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Identification of alternative splicing networks defining embryonic stem cell ide...

Identification of alternative splicing networks defining embryonic stem cell identity "Adult, embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) possess the fundamental properties to self-renew while remaining pluripotent. These unique capacities are regulated by gene networks which expression is... ver más

28/02/2018

INSERM

100K€

Presupuesto del proyecto: 100K€

Líder del proyecto

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2018-02-28 No tenemos la información de la convocatoria

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1 Participantes

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Líder del proyecto

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 100K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto "Adult, embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) possess the fundamental properties to self-renew while remaining pluripotent. These unique capacities are regulated by gene networks which expression is tightly controlled at the epigenetic, transcriptional and post-transcriptional levels to insure proper stem cell fate decisions in response to developmental or environmental cues. Alterations of these networks in cancer stem cells (CSC) support their tumorigenic activity. Therefore, defining the molecular pathways that control the maintenance of self-renewal and pluripotency is not only important to understand normal development but could also improve the clinical potential of adult stem cells, ESCs and iPSCs, and reveal novel strategies to target CSCs. Our objective is to identify novel mechanisms controlling the genetic programs that define the fate of ESCs. Along this line, we recently revealed a central role for alternative splicing (AS) in the regulation of the core ESC pluripotency regulatory circuitry. AS affects over 95% of multi-exon human genes and regulates gene expression by promoting transcriptome and proteome diversity. Although ESCs display a high degree of transcriptome complexity and express a large number of isoforms of unknown function, the extent and significance of AS contribution to this functional diversity remain largely unclear. We propose to characterize molecular pathways that modulate AS programs and reshape the landscape of gene regulation which controls the pluripotency and self-renewal capacities of stem cells. More precisely, we will: 1- Identify splicing factors that control conserved AS events in mouse ESCs and support the maintenance self-renewal and pluripotency; 2- Characterize AS and gene networks coordinated by these essential factors to reshape the transcriptome of mouse ESCs; 3- Define the regulatory code underlying the in vivo regulation of ESC-specific AS networks by these splicing factors."

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