Unraveling the Transcriptional Heterogeneity in Human Colon Cancer: Potential New Insights regarding Pathobiology and Treatment

Abstract

In a recent hallmark report in Nature Biotechnology , Dalerba and colleagues from Stephen Quake's and Michael Clarke's laboratories at Stanford demonstrated the power of single-cell expression analysis for the elucidation of human tissue function and pathology (1). They made a detailed molecular dissection of healthy and colon cancer tissue to address fundamental questions about tumor heterogeneity and clonality. This pioneering and impressive work shows that much is to be gained by resolving the cellular heterogeneity of tissues. This more detailed characterization of normal and diseased tissue can provide valuable insights into cancer pathobiology that can be used for improving diagnosis and stratification of patients, and it has the potential to lead to new insights regarding treatment. Dalerba and colleagues first made a single-cell suspension of healthy colon tissue. They used fluorescence-activated cell sorting with established differentiation markers to isolate and separate well-differentiated epithelial cells at the top of colon crypts from the more immature stem cell–like cells at the bottom of colon crypts. They then performed single-cell quantitative PCR analyses …