Lab focus – Understanding post-transcriptional regulation in cell differentiation and its alteration in neurodegenerative diseases
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.