The mammalian liver performs critical functions for maintaining metabolic homeostasis. These functions are carried out by hepatocytes operating in repeating anatomical units termed liver lobules. The liver lobule is polarized by centripetal blood flow, which creates gradients of nutrients, hormones and oxygen. In line with this graded microenvironment hepatocytes at different lobule coordinates sub-specialize in distinct functions. We study how this spatial division of labor within the liver lobule can serve to bring about optimal tissue function in face of these long-range constraints. An additional puzzling feature of the mammalian liver is its polyploidy. In contrast to most tissues in our body, which are composed of diploid cells, the liver consists of a mixture of diploid, tetraploid and octoploid cells. We are studying the physiological significance of liver polyploidy using single molecule imaging methods.
Spatial division of labor in the mammalian gut
Our intestines are lined with a single layer of epithelial cells that forms a highly folded structure. Cells are constantly emerging from deep stem-cell harboring crypts and migrate along the walls of protrusions called villi until they reach their tips, where they are shed off into the lumen. Using spatially resolved single cell RNA sequencing, we found that epithelial cells constantly change their function as they migrate along the villi walls, specializing in distinct tasks at different villi heights. We study the design principles of these zonated expression programs, the mechanisms that shape them and their changes in diverse metabolic disease.
Shed Cell Transcriptomics for Characterization of Digestive Tract Pathologies
The human digestive tract sheds massive amounts of cells every day. We found that these cells remain viable and can be transcriptionally profiled to yield valuable information on human pathophysiology. We characterize shed cells in fecal matter to characterize major human digestive tract pathologies, including inflammatory bowel diseases, colorectal cancer and celiac disease.
