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Functional analysis of Alternative Polyadenylation during neuronal differentiation at single cell resolution

Project description

Following a stem cell on its journey to becoming a neuron

The Human Genome Project identified all the genes present in the human genome, providing a list of building blocks that make us human. However, how those blocks are combined – which genes are expressed when and in which cells – is critical to identifying functions and it is particularly important during stem cell differentiation. The EU-funded SCAPA project plans to add its piece to the puzzle, shedding light on gene expression during differentiation of neuronal cells. Scientists are using high-tech methods to track a well-known pathway controlling gene expression, alternative polyadenylation, that can affect the availability of RNA binding sites. Analyses could point to molecular targets controlling gene expression during neuron development with exciting potential for new therapies.


Understanding how stem cells differentiate into the myriad of cell types that compose an organism is a fundamental question in biomedical sciences. The recent development of single-cell transcriptomic techniques has already allowed the study of the cell composition of organs and tissues, developmental stages, and even whole adult organisms. Yet, in most cases, these studies are primarily descriptive and often provide little insight into the mechanisms regulating gene expression during cell differentiation.
Here, I propose to study the role of alternative polyadenylation (APA) and associated RNA binding proteins (RBPs) in neuronal differentiation. For this purpose, I will: (i) develop new computational tools to detect and quantify APA events from single-cell transcriptomics data; and (ii) perform a single-cell-based functional CRISPR screen. The results obtained from this study will provide an in depth analysis of the changes in gene expression and APA during neuronal differentiation at a single cell resolution and identify dozens of APA targets specifically associated with individual RBPs.
Together, this study will provide a solid molecular knowledge of the role of APA in neural differentiation, enabling the development of new personalized medicine therapies, which is in compliance with the Horizon H2020 Health demographic change and wellbeing programme.


Net EU contribution
€ 160 932,48
Carrer doctor aiguader 88
08003 Barcelona

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Este Cataluña Barcelona
Activity type
Research Organisations
Other funding
€ 0,00