The mechanisms that define cell identity in complex organisms are still largely unknown. Most efforts have been focused on understanding how a few transcription factors direct cell differentiation in particular circumstances, such as during development or in cancer. However, many post-transcriptional processes, which are essential for defining the final transcript repertoire in a cell, have been overlooked and their role in establishing this identity is much less understood. In the lab, we want to understand how post-transcriptional regulatory processes, and in particular alternative polyadenylation, are coordinated at the individual cell level and how they contribute to the differentiation of cells both in health and disease conditions.
By combining single-cell transcriptomics with cellular reprogramming we can characterize at the molecular level how gene expression and post-transcriptional regulation are altered in several conditions and which is their contribution to the development if neurodegenerative diseases. By differentiating iPSCs to different types of neurons and other neural related cells, we can now study the differentiation process globally and identify all the gene expression changes responsible for the differentiation of individual cell types. Additionally, by comparing the differences in the differentiation of patient-derived and healthy iPSCs cells, we can identify the altered gene pathways that explain the onset and the progression of the disease.
The molecular mechanisms responsible for the development of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, are still largely unknown. We want to investigate how the basic molecular biology mechanisms involved in the regulation of RNA are altered in neurodegenerative diseases. This research will likely contribute to identify new targets for the development of new diagnostic tools and personalized medicine interventions.
NEUROSCAP: Role of alternative polyadenylation in neuronal differentiation and its implication in the development of Alzheimer’s disease at the single cell resolution. Proyectos de I+D+i Retos Investigación. Ministerio de Ciencia, Innovación y Universidades (2020-2023).