Cell-type-resolved alternative splicing patterns in mouse liver

Abstract

Alternative splicing (AS) is an important post-transcriptional regulatory mechanism to generate transcription diversity. However, the functional roles of AS in multiple cell types from one organ have not been reported. Here, we provide the most comprehensive profile for cell-type-resolved AS patterns in mouse liver. A total of 13,637 AS events are detected, representing 81.5% of all known AS events in the database. About 46.2% of multi-exon genes undergo AS from the four cell types of mouse liver: hepatocyte, liver sinusoidal endothelial cell, Kupffer cell and hepatic stellate cell, which regulates cell-specific functions and maintains cell characteristics. We also present a cell-type-specific splicing factors network in these four cell types of mouse liver, allowing data mining and generating knowledge to elucidate the roles of splicing factors in sustaining the cell-type-specialized AS profiles and functions. The splicing switching of Tak1 gene between different cell types is firstly discovered and the specific Tak1 isoform regulates hepatic cell-type-specific functions is verified. Thus, our work constructs a hepatic cell-specific splicing landscape and reveals the considerable contribution of AS to the cell type constitution and organ features.