Podcast Interview: Jennifer Lippincott-Schwartz - Proceedings of the ...

More broadly, I’m interested in what imparts a cell’s identity: why is your liver cell a liver cell
and your heart cell a heart cell, and why are they normally really stable? Why are they in those
conditions for life in most cases? Can we change that cell identity? That was the surprising thing
with induced pluripotent cells, it turns out that you can change cells’ identity with a relatively
small manipulation of just a few factors. I think you’ll find in the future that there will be a lot of
examples of cells changing identity, not back to a ground state, not back to the pluripotent state,
but between different cell types in the body.
Question: Are there any instances where what you have seen has surprised you?
Thomson: I guess the biggest surprise for the field, and in my lab also, is reprogramming. Dolly
[the sheep] was cloned about a year before—or at least the publication was a year before—
human embryonic stem cells were published by my lab. The two are already paired in the public
imagination from that early time. The message from Dolly was not that you can clone sheep, and
it was not that you could do somatic cell nuclear transfers and make an embryonic stem cell, it
was that transfecting stuff could reprogram an adult cell into an embryonic cell. It was only a
matter of time before people would identify that transfecting stuff. The surprise was that it
wasn’t as complicated as everybody thought. I would have guessed that it was 50-100 factors,
and it turns out that 2-4 is sufficient. But the bottom line is that a very small number of factors
can completely change the developmental state of a cell. That was unanticipated.
Question: How and why do stem cells choose to differentiate into different types of cells?
Thomson: Basically, cells talk to each other through external signaling molecules, the things
that diffuse between cells or which are linked to the cell surface, and depending on how those
signals are emitted and received, cells can turn into new cells. So for stem cells in tissue culture
dishes, we can look at all that developmental biology and say, what growth factor does this in a
normal embryo, and we can try that in a tissue culture dish, and often they are the same
molecules that can do the same thing.
Question: How do you feel to be elected into the National Academy of Sciences?
Thomson: It’s a good feeling. It means that you’re publicly accepted. An awful lot of what has
driven the publicity in stem cell research is hype, but it certainly means more to be accepted by
your peers and recognized by your peers, so it’s a big deal.
Question: Thank you very much for your time.
James Thomson is the director of regenerative biology at the Morgridge Institute for Research
and the John D. MacArthur professor at the University of Wisconsin School of Medicine and
Public Health. He was elected to the National Academy of Sciences in 2008.