Louis Faure, BSc
Department(s): Department of Neuroimmunology (Center for Brain Research)
Position: PHD Student
Location: Spitalgasse 4
During development, neural crest cells (NCC) are a transient group of cells that emerges from the dorsal part of the neural tube. This population of cells is fascinating because of their long range migratory capacity, as well as their stem cell like properties: they are responsible for the emergence of diverse cell lineages, such as Schwann cells, melanocytes, craniofacial cartilage and bone, sensory, enteric and sympathetic neurons. My PhD project aims at reconstructing the tree of cell fate decisions of NCC during mouse development, and at exploring the heterogeneity of their subsequent glial and neuronal progenitors.
We use genetical lineage tracing tools, in which we combine an inducible Cre expressed in a cell type of interest with a Cre-activated fluorescent reporter, allowing us to restrict our study to specific NCC populations and their progeny. On this selected population, we perform single-cell RNA sequencing in order to obtain the transcriptional identity at the level of a single cell. Dimensionality reduction and clustering methods are used to classify cell types. Regulatory networks and transcription factor activity are inferred using databases of known interactions. Cell to cell communications are explored using databases of known ligand-receptor pairs. To reconstruct the tree of fate decisions, we carefully sample several developmental time points and locations in the embryo in order to obtain smooth transitions and bifurcations in transcriptional space. Recapitulating these paths is performed by pseudotime analysis, a class of computational techniques which aims at mapping the highly dimensional single cell data on to a series of one-dimensional quantities, called pseudotimes. This approach allows us to recover the temporal dynamic changes of our studied system and treat them as time-series. Key gene markers for bifurcations are extracted for biological interpretations, which are then validated experimentally using technique such as immunostaining and RNAscope.
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