Single cell heterogeneity in the mammalian liver
Speaker: Shalev Itzkovitz, Department of Molecular Cell Biology, Weizmann Institute of Science
The mammalian liver performs critical functions for maintaining organismal homeostasis. These functions are carried out by hepatocytes operating in repeating anatomical units termed liver lobules. Centripetal blood flow creates gradients of nutrients, hormones and oxygen along the lobule radial axis. In line with this graded microenvironment, hepatocytes at different lobule coordinates sub-specialize in distinct functions. We combine single molecule transcript imaging in intact liver tissue with single cell RNAseq to reconstruct the global division of labor of all liver genes. Using nascent transcript imaging we find that many liver genes are expressed in transcriptional bursts, a phenomenon that can lead to large variability in transcript content between hepatocytes operating at the same lobule layer. We identify three mechanisms to reduce this burst-associated variability – coordination of burst frequency and mRNA lifetime, liver polydploidy and nuclear retention of mature transcripts. These mechanisms ensure global spatial heterogeneity among different lobule layers while minimizing the stochastic effects of transcriptional bursts.
This seminar is part of a seminar series hosted by SciLifeLab Fellows
Date: Oct 20
Venue: Air&Fire auditorium, SciLifeLab Solna
Host: Magda Bienko