RNA splicing is a hierarchical supernetwork that co-operates to drive osteoblast differentiation

Angel Liang⁰
(0) UNSW Sydney

Find me on Tues Nov 24th, 1:40-3pm AEDT in Remo, table 49

Abstract
Splicing is essential for the proper expression of mature messenger RNA (mRNA) transcripts in eukaryotes. A growing body of evidence shows alternative splicing of transcripts to be widespread and important for normal cell development and differentiation, where transitions from immature isoforms into their mature counterparts have been demonstrated in literature. Our study sought to understand the functions of alternative splicing in human mesenchymal stem cells (hMSCs), a type of multipotent adult stem cells with great therapeutic promise but severely unrealised due to an incomplete understanding of their stem cell maintenance and differentiation processes. Using Illumina short-read RNA-Seq, we explored the extent to which the landscape of mRNA splicing is changing and regulated as hMSC-TERT4 cells differentiate into osteoblasts, the cells which build bone. By integrating proteome, phosphoproteome and single-cell RNA-Seq data, we discovered that alternative isoforms not only have functional consequences in both the transcriptome and proteome, but can also demarcate homogenous cell sub-populations. Our findings represent a major advance in the knowledge of developmentally regulated splicing, with implications for the selection criteria of the “best” type of hMSCs to use in cell-based therapies for wound healing and bone regeneration.