Purchased with Pelotonia funding support, it’s called a 10X Genomics Chromium Controller, a sophisticated machine that, along with other complementary equipment within the GSR, is helping scientists understand the complexities of human biology more fully than ever with the goal of applying that knowledge to targeted therapies based on the molecular characteristics of individual cancers.
10X Genomics, the company that produces the Chromium Controller, says this instrument, together with assay-specific kits, is enabling researchers to “go beyond traditional gene expression analysis to characterize cell populations, cell types, cell states and more on a cell-by-cell (or single-cell) basis … providing a comprehensive, scalable solution for cell characterization and gene expression profiling of hundreds to tens of thousands of cells,” including rare cell types.
The GSR, which is now combined with the Genomics Services Laboratory at Nationwide Children’s Hospital, is one of 20 shared resources available to cancer researchers at Ohio State. The GSR provides a centralized source of high-throughput genomics technologies, offering instrumentation and expertise for DNA and RNA analysis using sequencing, genotyping, real-time PCR (a molecular biology lab technique based on the polymerase chain reaction) and other services. The GSR is led by director Richard Wilson, PhD, and co-director Amanda Toland, PhD. Both are members of the OSUCCC – James.
Pearlly Yan, PhD, one of two technical directors of the GSR, says the most popular assay for the 10X Genomics system at Ohio State is single-cell transcriptome analysis. Transcriptome refers to the entirety of messenger RNA molecules in the genes of an organism.
“A lot of people are very excited by this assay,” says Yan, a research assistant professor in the Division of Hematology at Ohio State and member of the Leukemia Research Program at the OSUCCC – James. “Several groups of scientists have talked to us about it. We already have embarked on 20 studies and finished 12.”
Yan says the 10X Genomics system offers advanced single-cell analysis that, as opposed to bulk cell sequencing, gives investigators a sharper and more refined look at cellular biology, benefiting both basic science investigators and translational researchers who apply discoveries to clinical care.
One key area of translational study for the 10X Genomics system, she says, is cancer recurrence.
“Often when therapy fails, it’s not due to the full-blown mature cancer cells not responding to therapy, but rather the evasion of quiescent stem or progenitor cells (earlier lineage of mature cancer cells) from the treatment,” she explains. “Chemotherapy targets rapidly growing cells. The stem/progenitor cells are slow growing. They may also have gained additional genomic alteration(s), thereby protecting them from treatment effects. They then are poised to become full-blown cancer cells later.”
However, through single-cell analysis (sequencing), scientists can examine all types of individual cells or cell populations — including the stem/progenitor cells — and identify their characteristics, hoping to find weaknesses that can be therapeutic targets.
“They want to discover the Achilles’ heel,” Yan says. “That’s what this is all about. When we do bulk sequencing, most of what we see are the bulk cancer cells, along with other material that infiltrates the bulk cancer. We see very little of the important stem/progenitor cell populations, but they can be revealed through single-cell analysis.
"The most important thing the 10X Genomics system does for translational investigators is to identify the types of cells in the tissue of interest,” Yan adds. “Basically when a patient’s cancer recurs, we want to see the cell populations and their gene profiles within the tumor.
“The software that comes with the 10X system, as well as other open-source software, will tell the researcher the hallmark of any particular group of cells — the fine composition — so they can be examined further. If anything suspect is found in these groups, the researcher can validate the 10X findings by other means to determine the true cause of disease recurrence.”