Iso-Seq SMRT Grant Winner to Study Alternative Splicing in Neurons

Xiaochang Zhang, an assistant professor at the University of Chicago, is poised to get a powerful new data set to help his team understand the role of alternative splicing in brain development. His project, entitled “Uncovering mRNA splicing diversity in cerebral cortex development,” was selected as the winner of the 2018 Iso-Seq SMRT Grant Program. Sequencing for this project will be carried out by our Certified Service Provider RTL Genomics. We caught up with Xiaochang to learn more about his research and how SMRT Sequencing data will make a difference.
Q: What’s your research focus?
A: We are interested in the impact of alternative RNA splicing in neocortex development and disorders, and we are excited about the opportunity to use long-read sequencing to further address this question. Enormous neuronal cell diversity has been described, and it is speculated that the secret of neuronal cell diversity is partly hidden in the heterogeneity of neural progenitor cells. Post-transcriptional mRNA metabolism such as alternative splicing presents another layer of gene regulation and dramatically increases protein diversity. Indeed, work from others and us showed that alternative pre-mRNA splicing is wide spread in developing mouse and human brains, and tight regulation of cell type-specific RNA splicing is required for human brain development. Characterizing mRNA isoforms with long-read sequencing will give us a unique chance to understand how the brain is built – we’re really excited about this.
Q: How have you pursued this prior to long-read sequencing?
A: We did bulk RNA sequencing with mouse brain cells and found hundreds of alternatively spliced exons between neural progenitor cells and post-mitotic neurons. We further analyzed a single-cell data set of fetal human brain cells and identified consistent RNA splicing changes between cell types. However, it is hard to obtain a full picture of alternative RNA splicing with short-read sequencing for genes that have multiple alternatively spliced exons. Long-read sequencing will be superior to uncover complex splicing isoforms.
Q: What do you hope to learn with the SMRT Sequencing data?
A: Single Molecule, Real-Time (SMRT) Sequencing can sequence single molecules of the longest human messenger RNAs. We are excited to directly detect the actual full-length mRNA isoforms among different brain cell types with SMRT Sequencing. We will compare long-read sequencing results with our current datasets, and try to uncover complex splicing isoforms that are previously unobservable. With this SMRT Grant we hope to get a better view of alternative RNA splicing in brain development.
 
We’re excited to support this research and look forward to seeing the results. Check out our website for more information on upcoming SMRT Grant Programs for a chance to win SMRT Sequencing. Also, thank you to our co-sponsor RTL Genomics for supporting the Iso-Seq SMRT Grant Program!