Fei Chen and Jason Buenrostro

For more than 20 years, scientists have been able to unravel the sequence of the human genome, the precise recipe of everyone’s DNA. That has led to incredible advances in discovering genes responsible for countless diseases. But within the last five to seven years, new and more sophisticated research tools have emerged. Known as single-cell genomics, these tools enable scientists to peer into individual cells – ranging from skin, nerve, muscle, immune cells, and even to cells that haven’t been discovered before – to learn more about how they function.

Two of the leaders in this young field – Jason Buenrostro, PhD and Fei Chen, PhD – lead laboratories within Harvard’s Department of Stem Cell and Regenerative Biology. They have developed some of the most influential single-cell genomics tools used today by researchers worldwide, helping to move this previous niche area of biology into a cornerstone of research.

“The cells across our various human tissues are diverse and it’s extremely valuable to understand how all of the cells are changing as we develop, grow, and age,” Buenrostro explains. “Single-cell sequencing has allowed us to do that.”

Single-cell genomics provides detailed information about our DNA and RNA – the instructions carried from DNA to make proteins. It also provides clues into influences, known as epigenetic modifications, which decide if a gene will be turned on or off in each cell. Researchers like Buenrostro and Chen, and many others, use this information regarding what is within the individual cells to better understand how cells are changing in normal processes as well as in those associated with disease.

“If you think about it, every cell in the body has the same genome,” says Chen. “But each type has to do different things.” So what are the unique components of each cell that tells it to function in a particular way? And what regulates that? If you pored over all the contents of a tissue, it would be impossible to answer these questions when looking at a mixture of cells, Chen explains. “You need to use single-cell genomics to reveal the diversity that exists within tissues and organs – including the many cell types, subtypes, and states the cells are in and how they interact, change, and evolve.”

The power of single-cell genomics can also be attributed to advanced new computational tools to interpret and analyze all the data points – an area where Buenrostro and Chen also contribute. Having the tools to both sequence individual cells and understand overflowing data stream has matured thinking in the field to ask more pointed, powerful biological questions. Questions like: Can we discover a new type of cell that we didn’t know existed? (answer: yes) and How do cells change in their function over time or due to disease?

“We and others are grappling with this treasure trove of different functions that an individual cell type might have – and making any tools broadly usable – so they can be used across virtually any scientific area involving cells, which is all of life,” says Buenrostro.