Cancer stem cells identified in single-cell study of brain tumors

A new study of oligodendroglioma at single-cell resolution suggests that stem cells may drive cancer proliferation.

By Veronica Meade-Kelly

November 2, 2016

Credit: Image by Lauren Solomon, Broad Communications. Micrograph courtesy of Nephron, Wikimedia Commons.

Researchers used single-cell genomic analysis to look at the individual cells at work in oligodendroglioma, a relatively slow-growing but incurable form of brain cancer.

A new study from researchers at the Broad Institute of MIT and Harvard and Massachusetts General Hospital used a single-cell genomics approach to look at the individual cells at work in oligodendroglioma, a relatively slow-growing but incurable form of brain cancer. The study, which was published this week in Nature, identified the presence of cancer stem cells for the first time in these tumors and suggested they may play a key role in their growth.

Previous work had suggested that stem-like cells could be responsible for the aggressiveness of some brain tumors, such as glioblastoma. However, more evidence was needed, especially in tumors early in their development. This led to the team’s work in oligodendroglioma: to get a better picture of the complexion and hierarchy of the cells at work in this type of cancer, the team used single-cell RNA sequencing methods pioneered at the Broad to analyze gene expression in over 4,000 cells from six patient tumors.

The study revealed that a subpopulation of these cells did, indeed, possess neural stem cell gene expression signatures, while the majority of cancer cells followed patterns associated with maturation and differentiation. Additionally, the team found that the stem cells accounted for almost all of the proliferating cancer cells in these tumors. Importantly, the authors observed that the same stem cells and differentiated cells were found in cells with different genetic mutations in these tumors, with stem cells fueling tumor growth in each case. This could mean that targeting these cancer stem cells may help inhibit tumor growth.

This work was led by co-senior authors Mario Suvà, an associate member at the Broad Institute and assistant professor of pathology at Massachusetts General Hospital and Harvard Medical School, and Broad core institute member Aviv Regev, director of the Klarman Cell Observatory and Cell Circuits Program at Broad Institute. Itay Tirosh and Andrew Venteicher, researchers in the Regev and Suvà labs, respectively, were co-first authors.

To learn more, read this Massachusetts General Hospital press release.