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Impact of microbiota on spatial gene expression along the 3D colonic barrier
Spatial organization at the cellular level is a fundamental aspect of complex life, orchestrating intricate biological processes with remarkable precision. This organization allows cells to efficiently exchange nutrients and signals, crucial for the proper functioning of multicellular organisms. Being able to describe the spatial landscape of the cells is hence essential to obtain a better understanding of tissue function. The human intestine is an example of a complex and dynamic tissue, highly regenerative and organized in 3-dimension (3D). The colonic epithelial barrier is known to have a precise spatial cell organization with a cell differentiation along the crypt axis. Many parameters act on the colon homeostasis and architecture and among them the gut microbiota is one of the key players. How this spatial organization of cell identity is maintained in the human colon and what is the impact of the microbiota is the central objective of this project. We will use organ-on-chip technology combined with human colonic organoids to recapitulate the hallmark of this 3D organized colonic barrier. These colon-on-chips will be used to develop a method to perform a spatial RNA profiling adapted to 3D-organized thick samples (smFISH). Once the spatial transcriptomic of colon-on-chip will be done, we will investigate the role of the microbiota component by using two strategies: either treating the barrier with microbiota metabolites SCFAs or co-cultivating the colon-on-chip with two probiotic bacteria (Lactobacillus rhamnosus and Bifidobacterium longum). The project will also enable the scientific community with a new method to perform spatial transcriptomic on thick tissues.
