Single Cell Heterogeneity in the Mammalian Liver
Event details
| Date | 09.11.2016 |
| Hour | 11:00 |
| Speaker | Prof. Shalev Itzkovitz, Weizmann Inst. of Science, Rehovot (IL) |
| Location | |
| Category | Conferences - Seminars |
BIOENGINEERING SEMINAR
Abstract:
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.
Bio:
CURRENT POSITION
Senior Scientist, Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
EDUCATION
Massachusetts Institute of Technology, Cambridge MA, USA:
Postdoc at the departments of Biology and Physics 2009-2012
Weizmann Institute of Science, Rehovot, Israel:
Postdoc at the department of Computer Science and Applied Mathematics, 2007-2009
Ph.D. in Biology with honors, 2002-2006
Technion, Haifa, Israel:
M.Sc. Electrical Engineering, 1996-2000
Hebrew University, Jerusalem, Israel:
B.Sc. in Physics and Mathematics with honors, Talpiot Program, 1993-1996.
Abstract:
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.
Bio:
CURRENT POSITION
Senior Scientist, Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
EDUCATION
Massachusetts Institute of Technology, Cambridge MA, USA:
Postdoc at the departments of Biology and Physics 2009-2012
Weizmann Institute of Science, Rehovot, Israel:
Postdoc at the department of Computer Science and Applied Mathematics, 2007-2009
Ph.D. in Biology with honors, 2002-2006
Technion, Haifa, Israel:
M.Sc. Electrical Engineering, 1996-2000
Hebrew University, Jerusalem, Israel:
B.Sc. in Physics and Mathematics with honors, Talpiot Program, 1993-1996.
Practical information
- Informed public
- Free