Abstract

Single Cell Tumor Transcriptomics

Shyam Prabhakar, Associate Director/Integrative Genomics and Group Leader, Genome Institute of Singapore

With the advent of single-cell genomic technologies, we can now begin to understand the heterogeneity of tumors. Initial studies in this rapidly expanding field focused on DNA sequencing to detect somatic mutations in individual cells. A second wave of studies is now building, and it will address functional heterogeneity within tumors by profiling single-cell transcriptomes. We have analyzed over three thousand single-cell transcriptomes from primary lung and colon tumors and matched controls. Using a novel clustering algorithm that minimizes noise and technical bias, we then identified multiple cell types de novo within the tumor and normal samples. Variation in gene expression within and across these cell types provided a unique window into tumor-specific biology, allowing us to investigate the prevalence of cancer stem cells and the epithelial-mesenchymal transition. We also used our single cell data to redefine differentially expressed gene sets in a cell-type-specific manner and reveal signaling interactions between fibroblasts, immune cells and epithelial cells within tumors. Going forward, we see single-cell transcriptomics becoming an essential tool for cancer biology, biomarker discovery and personalized oncology.