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Dissecting the role of sperm transcriptome dynamics in intergenerational inheritance through native RNA nanopore sequencing

Project description

Diet-based regulation of sperm RNA

Emerging evidence underscores the importance of environmental factors such as stress, diet and toxins on the epigenetics of mammalian sperm. RNA is considered to carry such epigenetic information across generations and regulate the metabolic health of offspring. Funded by the European Research Council, the EpiSperm project aims to delineate the RNA modifications that affect RNA transcriptomic and epigenetic dynamics in sperm using a novel sequencing technology. Researchers will obtain a holistic view on RNA dynamics at the single-cell level. Moreover, they will unveil candidates that can transmit diet-induced paternal phenotypes to the next generation.

Objective

Mammalian sperm RNA is increasingly recognized as an additional source of paternal hereditary information beyond DNA. Environmental inputs, such as diet and stress, can reshape the sperm RNA signature and induce offspring phenotypes that relate to paternal environmental stressors. However, how, when and to what extent sperm RNA populations change, and what is the role that RNA modifications and other post-transcriptional regulatory layers play in shaping sperm RNA dynamics, remains poorly understood. Here, we propose to characterize the dynamics of RNA populations during sperm formation and maturation using native RNA nanopore sequencing. This technology is suited to provide an integrative and comprehensive view of the transcriptome, epitranscriptome, degradation patterns and tailing dynamics simultaneously, and with single molecule resolution. We will establish novel library preparation methods that can capture the full sperm (epi)transcriptome, and will capitalize on our recently developed algorithms to map and quantify RNA modifications in individual RNA molecules. We will then apply these methods to reveal how paternal dietary exposures affect sperm RNA populations and the metabolic phenotypes of their offspring, and test whether the novel identified RNA candidates can transmit diet-induced paternal phenotypes to the subsequent generation. Finally, we propose to expand our previous work on direct RNA multiplexing to establish single cell direct RNA nanopore sequencing, to characterize the diversity and heterogeneity of the sperm RNA (epi)transcriptome at an unprecedented single cell and single molecule resolution.

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(opens in new window) ERC-2021-STG

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Host institution

FUNDACIO CENTRE DE REGULACIO GENOMICA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 499 428,00
Address
CARRER DOCTOR AIGUADER 88
08003 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
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Total cost

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€ 1 499 428,00

Beneficiaries (1)

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