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Colas Droin, Jakob El Kholtei, Keren Bahar Halpern, Clémence Hurni, Shalev Itzkovitz, Félix Naef (EPFL, Lausanne)
The liver plays a key role in maintaining the body metabolic homeostasis. Its physiological functions are temporally orchestrated by the interplay of the endogenous circadian clock, systemic signals and feeding rhythms. The liver is also structured in space. It is composed of repeating anatomical units termed lobules, in which blood flow creates gradients of oxygen and morphogens. This gradient leads to a differential gene expression and dictate the physiological status of hepatocytes, a phenomenon called zonation. Here, we use single-cell RNAseq, to reconstructed mRNA expression profiles levels across space and time. We reconstructed the spatial gene expression profiles by inferring the position of each hepatocyte based on a previous genome-wide spatial reconstruction. We then developed a classification method to retrieve the spatial and temporal features of these profiles, enabling to find that about 30% of the genes are significantly zonated, 20% are rhythmic, and 10% are both temporally and spatially controlled. Together, this analysis presents for the first time a comprehensive overview of the temporal liver functions at the sub-lobular scale.