Transcriptomics and Functional Genomics Lab (TFGL)

Research Line 2: Transcriptional regulation at single-cell resolution

Inter-individual differences in gene expression observed at the tissue level can arise from tissue-specific expression changes, or cell type composition shifts. Single-cell technologies are a powerful tool to disentangle the contribution of each component by profiling the transcriptome of individual cells. The expanded scale of single-cell techniques now also offer the opportunity to investigate how donor characteristics (such as sex, age, genetic ancestry, or body mass index) or environmental conditions (such as immune stimulation or lifestyle) shape cellular composition, gene expression, chromatin accessibility, and alternative splicing at an unprecedented resolution.

Since January 2020, we are part of the steering committee of the single-cell eQTL Consortium, (https://eqtlgen.org/sc/participating.html) an ongoing international collaborative effort to study the genetic determinants of gene expression changes in immune blood cells from thousands of individuals using a meta-analysis framework. We expanded this statistical framework to study gene expression differences across individuals, including age, sex and genetic ancestry differences across immune cell types.

Research line 4:  Transcriptional regulation of ribosomal RNA and ribosomal proteins

Ribosomes are fundamental units of life and are the main cellular machinery to carry out protein synthesis. Ribosomes are formed by ribosomal proteins and ribosomal RNA, which both have refined regulation at the expression and post-transcriptional level, in an extremely complex assembly process. In recent years, the view of the ribosome has radically changed. Traditionally, the ribosome was viewed as a static cell machinery that carried out protein translation lacking any regulatory roles. Recently, it has been shown that ribosomes can be different between tissues and developmental time points and that these differences may play regulatory roles. Specifically, a handful of studies have suggested that ribosomes can differ in their ribosomal protein composition and this can have an impact on the pool of translated mRNAs. However, the extent of this ribosome heterogeneity and its functional impact is still unclear. In our lab, we recently found evidence that alternative splicing on ribosomal proteins may play a fundamental role in generating ribosome heterogeneity not only between tissues but also between human populations (Garcia-Perez et al. 2023). In addition, we also observed that studies on ribosomal RNA gene expression are extremely scarce, especially in humans. This is mostly due to the fact that ribosomal RNA represents 80% of the RNA in the cell and all RNA sequencing protocols deplete it and treat it as a contaminant. We are developing innovative computational approaches to rescue these discarded ribosomal RNA reads and study gene expression variation in ribosomal RNAs across individuals and tissues.