An Overview of Single Cell Technology, From Miller-Jensen Lab

07/22/2016

An expanding array of technologies are giving scientists a better look at single cells. In a recent journal article, Prof. Kathryn Miller-Jensen notes that researchers would do well to take advantage of these breakthroughs.

Cells, even when they’re genetically identical, react differently to the same cues. Until recently, researchers were limited to monitoring the “average” of cells, which meant that outlier cells and other important information were overlooked.

“What people started to appreciate was that if you could actually track biological events in live single cells, then you could get a better understanding of how a biochemical signal - what the cells are interpreting - translates into a response of interest,” said Miller-Jensen, assistant professor of biomedical engineering. 

In the journal Trends in Biotechnology, Miller-Jensen wrote a summary of some of the experimental tools available to researchers to probe single cells. She co-wrote it with her collaborator Prof. Suzanne Gaudet, Assistant Professor at Harvard Medical School.

It was more than 10 years ago when a critical mass of researchers became more aware of the differences between cells and interested in developing single-cell technologies to measure those differences. Miller-Jensen argues that single-cell data make it easier to apply an engineering approach to biological problems – that is, to study the cell as a machine.

“It’s a lot harder to figure out how a machine works if you’re averaging together a lot of machines,” she said. “Each cell has an input and an output, but if you average them together, a lot of information is lost.” Individual examination, though, puts researchers in a much better position to figure out the “wiring of the machine.” And by strategically altering that wiring, she said, new therapies could emerge.

The new technologies have already led to some important breakthroughs. A series of recent studies employed single-cell imaging to look at the efficacy of chemotherapy drugs, and possibly how the timing of the drugs could lead to better results.

“The variability in the population means that each cell might be affected differently by the same drug,” Miller-Jensen said. “There’s nothing genetically distinguishable about the cells per se, but the knowledge that individual cells respond differently means that some cells might be transiently ‘resistant’ and so we have to rethink how we apply treatments like chemotherapy.”

There are still some limitations to single-cell technologies. With live cells, for instance, researchers can only look at a handful of proteins at a time.  “But what you give up in the number of proteins you can measure, you gain by being able to look at the dynamics of a protein over time.”

More critical, she said, is getting more researchers to adopt the existing technologies. “The point of this article was to let people know what tools are there – what genetic tools, what microfluidic tools – and also how these tools are changing our understanding of the biology.”

Image of human T cell from National Institute of Allergy and Infectious Diseases (NIAID).