Portal de Periódicos da CAPES

Single-cell dissection of transcriptional heterogeneity in human colon tumors

2011; Nature Portfolio; Volume: 29; Issue: 12 Linguagem: Inglês

10.1038/nbt.2038

1546-1696

Piero Dalerba, Tomer Kalisky, Debashis Sahoo, Pradeep S. Rajendran, Michael E. Rothenberg, Anne Leyrat, Sopheak Sim, Jennifer Okamoto, Darius M. Johnston, Dalong Qian, Maider Zabala, Janet Bueno, Norma Neff, Jianbin Wang, Andrew Shelton, Brendan C. Visser, Shigeo Hisamori, Yohei Shimono, Marc van de Wetering, Hans Clevers, Michael F. Clarke, Stephen R. Quake,

Genetic factors in colorectal cancer

Not all cells in a tumor are alike, but our ability to characterize cancer heterogeneity in detail has been limited. Dalerba et al. use high-throughput single-cell expression analysis to define clinically relevant subpopulations in normal and cancerous colon tissue. Cancer is often viewed as a caricature of normal developmental processes, but the extent to which its cellular heterogeneity truly recapitulates multilineage differentiation processes of normal tissues remains unknown. Here we implement single-cell PCR gene-expression analysis to dissect the cellular composition of primary human normal colon and colon cancer epithelia. We show that human colon cancer tissues contain distinct cell populations whose transcriptional identities mirror those of the different cellular lineages of normal colon. By creating monoclonal tumor xenografts from injection of a single (n = 1) cell, we demonstrate that the transcriptional diversity of cancer tissues is largely explained by in vivo multilineage differentiation and not only by clonal genetic heterogeneity. Finally, we show that the different gene-expression programs linked to multilineage differentiation are strongly associated with patient survival. We develop two-gene classifier systems (KRT20 versus CA1, MS4A12, CD177, SLC26A3) that predict clinical outcomes with hazard ratios superior to those of pathological grade and comparable to those of microarray-derived multigene expression signatures.