single cell sequencing

In our age of specialization, today’s guest, Dr. Will Hwang of Massachusetts General, went against the trend and received three bachelor degrees in different fields.

Or is this the new trend?

Will says that despite the diversity of pursuits, there was a thread that ran throughout his life as a student. He always liked to look at things at the fundamental unit.

Perhaps this paradox in Will’s career is true for biology as well—that which exists between the broad interdisciplinary approach and the single-minded, reductive approach. Between a focus on cause and effect and the descriptive. If biology has been overly reductive in the past few years with the great genomic age, the trend now is to open up again. The spatial biology revolution is part of this new awareness.

Will is a physician scientist at Massachusetts General Hospital Center for Systems Biology Department of Radiation Oncology and Center for Cancer Research. He's also an assistant professor at Harvard Medical School and an associate faculty member at the Broad Institute. And he’s the lead author of the cover article of the August edition of Nature Genetics. The result of several years of work, the paper reveals the discovery of a new type of pancreatic cell subtype, a neuro-like cell progenitor cancer cell his group calls "NERP."

“Using single RNA nucleus sequencing paired with spatial whole transcriptome technology, we were able to identify a novel treatment resistant sub-type of pancreatic cancer which we have annotated as a neuro-like progenitor subtype. This has very important clinical relevance in terms of patient outcomes. It also has very unique spatial associations with other subtypes," says Will.

Will goes on to suggest the same cell type may also be present in other cancers, such as bladder cancer. What does the study mean for pancreatic cancer research going forward? What are the follow-up questions, for example, what are the drivers of this novel subtype? What does it mean for the treatment of pancreatic cancer patients? Will says he is now working to screen several existing drugs for treatment against the cells.

We finish up with Will's advice to young scientists that could apply to their science as well as their careers: be open to fields that may not be your specialty.

Vivek Bhalla is used to the question, what’s a nephrologist? When we admitted we’d never had one on the program, he made his own admission, saying that the kinds of people who became nephrologists are the kinds of people who don’t seek out the limelight.

But Vivek, an assistant professor of medicine at Stanford, is changing that and speaking out on behalf of his profession. And he’s very excited about what single cell sequencing has done for the study of the kidney.

“The people who developed single cell RNA sequencing probably weren’t thinking about kidney physiology or kidney disease when they developed it, but they developed a tailor made technique for nephrology," says Vivek.

Why? It has something to do with the fact that kidneys are made up of nephrons which in turn are made up of a sequence of specialized cells. Because there are so many kinds of cells that run next to each other, it is difficult to extract one type of cell from another.

“That has hampered our understanding of how each of these segments work and has slowed the field compared to other fields where an organ is much more homogeneous, such as the liver or the heart where the bulk of the tissue is made of cardiomyocytes. In the kidney there are fourteen different segments along the nephron."

Sounds great. So what new possibilities in the science and in clinical applications are opened up by all of this?