In this presentation, Sebastian Bergling, Senior Data Scientist at the Novartis 's presentation focused on the collaborative research on liver mechanisms, particularly metabolic liver zonation and regeneration using spatial transcriptomics. The collaboration involved the Novartis Genomics NGS team, Ulrike Neumann, Jan Tchorz's team, and Basel University's Luigi Terracciano's team.
The experiments aimed to dissect the mechanisms of metabolic liver zonation and regeneration. The Visium capture area, with a spot size of 55 microns, was relatively small compared to hepatocytes, capturing a mixture of different cell types.
The liver's core functional entity involved blood flow through the portal vein to the central vein, with hepatocytes performing position-dependent tasks. The research found a clear separation between periportal and pericentral hepatocytes in mice, but not as strong in human liver samples.
Activating the WNT pathway with R-spondin in mice showed increased WNT signalling and proliferation, disrupting the normal zonation and favouring pericentral gene expression. Upon liver injury, there was a ductular reaction driven by YAP, involving biliary cell proliferation and hepatocyte reprogramming. The research aimed to profile metabolic zonation and mechanisms of ductular reactions and hepatocyte reprogramming to understand pathways important for liver regeneration.
The presentation highlighted the differences in liver zonation between mice and humans, the effects of R-spondin treatment, and the mechanisms of liver injury and regeneration. The research aimed to provide insights into liver regeneration and potential therapeutic approaches.
