High-Parameter Single-Cell Analysis.

Thousands of transcripts and proteins confer function and discriminate cell types in the body. Using high-parameter technologies, we can now measure many of these markers at once, and multiple platforms are now capable of analysis on a cell-by-cell basis. Three high-parameter single-cell technologies have particular potential for discovering new biomarkers, revealing disease mechanisms, and increasing our fundamental understanding of cell biology. We review these three platforms (high-parameter flow cytometry, mass cytometry, and a new class of technologies called integrated molecular cytometry platforms) in this article. We describe the underlying hardware and instrumentation, the reagents involved, and the limitations and advantages of each platform. We also highlight the emerging field of high-parameter single-cell data analysis, providing an accessible overview of the data analysis process and choice of tools.

Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis.

Lung cancer is the leading cause of cancer deaths worldwide, with the majority of mortality resulting from metastatic spread. However, the molecular mechanism by which cancer cells acquire the ability to disseminate from primary tumors, seed distant organs, and grow into tissue-destructive metastases remains incompletely understood. We combined tumor barcoding in a mouse model of human lung adenocarcinoma with unbiased genomic approaches to identify a transcriptional program that confers metastatic ability and predicts patient survival. Small-scale in vivo screening identified several genes, including Cd109, that encode novel pro-metastatic factors. We uncovered signaling mediated by Janus kinases (Jaks) and the transcription factor Stat3 as a critical, pharmacologically targetable effector of CD109-driven lung cancer metastasis. In summary, by coupling the systematic genomic analysis of purified cancer cells in distinct malignant states from mouse models with extensive human validation, we uncovered several key regulators of metastatic ability, including an actionable pro-metastatic CD109-Jak-Stat3 axis.