How heterogeneous systems of cells constituting multicellular organisms establish, organize and achieve coordination persists as a central question in natural sciences. Whereas stochastic gene or protein expressions have clearly demonstrated their role in cellular heterogeneity and are widely studied (Wang and Bodovitz, 2010), the role of cell heterogeneity in the organization of multicellular organisms has been less interrogated. Addressing this question requires adequate tools that quantitatively study ensembles of cells individually rather than group of cells.

My research aims at addressing cell heterogeneity in dynamical and complex systems of cells using the hematopoietic system as a model of study. Strikingly hematopoietic cells (immune cells, platelets and red blood cells) compose over 90% of total human cells and correspond to approximately ten trillions of cells (Sender R, 2016). More importantly they all originate from the same cells, the hematopoietic stem cells (HSC), through a process called hematopoiesis. In addition, as immune and blood cells have a short life span (from hours to months) and can response to perturbations like infections, this process is highly dynamical. It is therefore an interesting and challenging model to study differentiation in a complex system at the single cell level.

To achieve this, we combine different experimental and mathematical/computational approaches of single cell tracing to study hematopoiesis in vivo. For example cellular barcoding is one of the lineage tracing approaches used by the lab. It simultaneously traces the in vivo differentiation of individual cells, allowing to reconstitute the relationship between cell lineages with single cell resolution. In this seminar, we will discuss some of our recent results using cellular barcoding in hematopoiesis.