SCAPA · Functional analysis of Alternative Polyadenylation during neuronal differentiation at single cell resolution
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-04-01 → 2021-03-31
- EU contribution
- €160,932
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Functional analysis of Alternative Polyadenylation during neuronal differentiation at single cell resolution
Understanding how stem cells give rise to all the cell types that compose an organism is a fundamental question in biomedical sciences. With the development of single-cell transcriptomics, now we can identify the genes expressed in individual cells and understand how much gene expression across cells. Furthermore, we can also use it to characterize the dynamic changes in gene expression with time and understand how cellular differentiation is regulated at the transcriptomic level. This technology has already been used to characterize the cell composition of organs and tissues, developmental stages, and even whole organisms. Yet, it has not been used to profile the function of gene regulatory mechanisms in cell differentiation. The aim of this project was to take advantage of the recently developed single-cell transcriptomics to understand the functional impact of regulatory proteins in the differentiation of neurons derived from mouse embryonic stem cells (mESCs). The results of this project will advance our knowledge on how gene regulation affects the differentiation of neurons and will provide specific information of some regulators. This information will be a steppingstone to better understand how different gene regulatory mechanisms influence neuronal differentiation. Ultimately, this information will be useful for the future development of personalized medicine therapies based on inducible pluripotent stem cells.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- FUNDACIO CENTRE DE REGULACIO GENOMICA · BarcelonaCoordinatorSpain
Links
Data: CORDIS, © European Union