Cellular crosstalk and metabolic regulation in advanced disease

Single-cell data from the Ravnskjaer group and other laboratories around the world start giving a broad overview of cells and cell states in diseased tissues. Cellular crosstalk in tissues during disease progression, however, remains poorly understood. A major reason for this lack of knowledge is the limited insights into the spatial organization of the various interacting cell populations.

Applying single-cell-resolved and various spatial techniques we here explore cellular crosstalk in human and murine NASH at single-cell resolution. We combine the powers of sequencing-based technologies and advanced microscopic analyses to identify and study specific interactions in intact liver tissue. Selected interactions are further characterized experimentally by pharmacological and genetic perturbation.

Description of the project by Ph.D. student Daniel Hansen

In this project special focus is placed on hepatic stellate cells (HSCs) and their interactive role in NASH and fibrosis development. We are investigating crosstalk between HSCs and other non-parenchymal liver cells including; sinusoidal endothelial cells and Kupffer cells. The project utilizes single-cell RNA-sequencing, spatial transcriptomics, and advanced imaging to better understand the cellular interactions in human and mouse liver. Transgenic mouse models are further used to comprehend the tissue plasticity of hepatic sinusoids and combines functional genomics and histological investigations to gain fruitful insights into disease development.