Datasets

Title	Dynamic remodeling of translation programs drives hepatocyte proliferation during liver regeneration
Organism
Number of Samples	12
Release Date	2017/10/25 00:00
Sequencing Types
Protocol Details

Title
Authors	Bangru S,Arif W,Seimetz J,Bhate A,Chen J,Rashan EH,Carstens RP,Anakk S,Kalsotra A
Journal	Nature structural & molecular biology
Publication Date	2018 Oct
Abstract	During liver regeneration, most new hepatocytes arise via self-duplication; yet, the underlying mechanisms that drive hepatocyte proliferation following injury remain poorly defined. By combining high-resolution transcriptome and polysome profiling of hepatocytes purified from quiescent and toxin-injured mouse livers, we uncover pervasive alterations in messenger RNA translation of metabolic and RNA-processing factors, which modulate the protein levels of a set of splicing regulators. Specifically, downregulation of the splicing regulator ESRP2 activates a neonatal alternative splicing program that rewires the Hippo signaling pathway in regenerating hepatocytes. We show that production of neonatal splice isoforms attenuates Hippo signaling, enables greater transcriptional activation of downstream target genes, and facilitates liver regeneration. We further demonstrate that ESRP2 deletion in mice causes excessive hepatocyte proliferation upon injury, whereas forced expression of ESRP2 inhibits proliferation by suppressing the expression of neonatal Hippo pathway isoforms. Thus, our findings reveal an alternative splicing axis that supports regeneration following chronic liver injury.
PMC	PMC6173981
PMID	30250226
DOI

Bangru et al. 2018 (PRJNA415722)