What Makes a Stem Cell a Stem Cell? Both stem cells and cancer cells have the unusual ability to renew themselves. So what lets a stem cell know it's a stem cell, and not a cancer cell? Stem cell researcher George Daley talks about the discovery of a protein that may help give stem cells their unusual multi-function abilities.
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What Makes a Stem Cell a Stem Cell?

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What Makes a Stem Cell a Stem Cell?

What Makes a Stem Cell a Stem Cell?

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JOE PALCA, host:

And now we shift gears and go into some very basic biology.

One of the things that make stem cells so interesting to scientists is their ability to shift forms becoming other cell types. Cancer tumor cells can do something similar and cancer cells and stem cells seem to share some of their inner mechanisms.

So what makes these two types of cells different from other cells? Well, the good person to ask that question of is George Daley. He's an associate professor of biology, chemistry and molecular pharmacology at Harvard Medical School and an associate professor of pediatrics at Children's Hospital in Boston. And he's one of the authors of a paper this week in the journal, Science, reporting on his lab's investigations into the proteins and triggers that regulate how a stem cell operates.

Welcome back to the program, George Daley.

Doctor GEORGE DALEY (Stem Cell Researcher; Associate Professor, Biological Chemistry and Molecular Pharmacology, Harvard Medical School; Associate Professor, Pediatrics, Children's Hospital Boston): Thank you, Joe.

PALCA: So - and if you want to ask questions about this, you're welcome to join us. And just remind you, the number is 800-989-8255, that's 800-989-TALK.

So, I mean, what's the premise here? Why are we talking about cancer cells and stem cells in the same breath?

Dr. DALEY: Well, you know, both of these types of cells are generated a lot of real excitement recently. Stem cells have now been made from skin cells by simply introducing a small number of genes. And what we think is going on there is essentially a dedifferentiation process taking a highly specialized cell and reverting it back to its sort of primitive origins as a stem cell.

Well, one of the proteins that's involved is called lin-28. And our group has recently shown that this protein is involved in regulating a class of small RNAs which don't actually make proteins themselves but regulate the expression of other proteins. Well, we were studying this protein lin-28 and we actually were thinking it was more relevant to cancer, and it turns out that it's relevant to both stem cells and cancer.

PALCA: We're talking with George Daley about a protein that seems to be important to decide the fate of cells. I'm Joe Palca and this is TALK OF THE NATION from NPR News.

And lin-28, if I remember right, was one of these magic factors that was able to take a normal skin cell and make it behave like an embryonic stem cell.

Dr. DALEY: That's right. So Jamie Thomson's group discovered this and reported it in November. Our group, which involves one of my graduate students, Srini Viswanathan, and a very talented junior faculty member, Richard Gregory, was studying this tendency for RNAs to be blocked in processing in embryonic tissues. And we discovered this protein. We had no direct idea it might be the same kind of protein that would reprogram skin cells. And interestingly enough, that was a project going on in a different part of my lab.

So when Jamie Thomson's paper came out, there was like this collective gasp in the group because all of a sudden, two very or seemingly disparate tracts of science in my own group were actually one and the same.

PALCA: And so what, I mean, tell me a little bit more about this lin-28. It's something to do with these microRNAs, is that right?

Dr. DALEY: You know, lin-28 has a long history. I think it was discovered about 20 years ago in worms. It was a gene which when disrupted in worms changed the sort of developmental timing of the organism. And then more recently, there's just been a couple of papers here and there which has seemed to suggest that if you express it in certain cells, it would actually promote their proliferation and maybe be involved in tumor agenesis.

So what's really been going on in the stem cell community is looking for genes that will turn these specialized cells like skin cells back into stem cells. And along the way, lin-28 fell out of these screens. Well, we've now provided the explanation for how lin-28 works. It seems to work by regulating the development of these very exciting and interesting classes, small RNAs called microRNAs.

PALCA: And is there an implication then for - I mean, it's always been a question, I suppose, that the cells that are embryonic stem cells - one of the tests to make sure they're really embryonic stem cells is that they can form these tumors that can have all sorts of tissue types in them. But that's always raised this, at least the possibility in my mind - I guess others as well - that somehow cells derived from these could be cancer-causing, is this part of understanding that process as well?

Dr. DALEY: Yes. Yes, in fact, it's very important for that process. So stem cells have very important properties that they replenish our tissues. They repair disease and destruction, but in doing that, they also have the possibility that if they become deranged, they can actually form tumors. And now we do appreciate that many classes of cancer arise from what are called cancer stem cells. That that can be either because the stem cells in the tissue undergo mutations which make them behave badly or in other instances, it's a - you get a more specialized cell which undergoes this kind of dedifferentiation process and making it more like a stem cell.

PALCA: George, we're going to have to take a break and - so hold that thought and we'll come back in about a minute or two and we'll finish the explanation, okay? Great.

So we're going to be talking more with George Daley about stem cells and how they are similar to and different from cancer cells, so stay with us.

This is TALK OF THE NATION from NPR News.

(Soundbite of music)


We're talking this hour about stem cells with George Daley of Children's Hospital Boston and he's also affiliated with Harvard Medical School.

And George, you were in the midst of a discussion of the process by which stem cells can - and become cancer cells or it might even be the cause of cancer in some cases, then we had to stop, so can you back up a little and take another run at it?

Dr. DALEY: Sure.

PALCA: Okay.

Dr. DALEY: Well, I think we're speaking to the point that stem cells have in some instances a similarity-ness(ph) to cancers. The most versatile stem cells, the embryonic and the pluripotent stem cells are immortal, that is they grow forever, and that's a property which is shared very closely with cancers.

Now, cancers are immortal and they don't differentiate normally. Stem cells are immortal and typically, if they're in the right environment, will specialize, will differentiate, will become functional tissues. So what we're learning is that the same kinds of genes that can help us make stem cells - genes like lin-28 or genes like MIC(ph) - may also be similar genes to those that when they're disregulated(ph) make cancers. So these kinds of studies of stem cells and cancers are actually turning out to reveal aspects of common biology, pathways that may be similar to both.

PALCA: Cool. Very interesting.

All right, I think we have time for one call, so let's try Elaine(ph) - I'm sorry - Kate(ph) in Greensboro, North Carolina.

Kate, welcome to the program.

KATE (Caller): Thank you very much. I was just reading an article about using the mouse testicular cells and turning those into cancer cells, I mean - excuse me - into stem cells. And I'd like to get Dr. Daley's viewpoint on that research and how he could expand his own research in that direction, and I'll take my comments off the air.

PALCA: Okay, Kate, thanks.


Dr. DALEY: That's a fascinating area of experimentation. It's part of this now growing tradition of being able to take cells from the body whether they're skin cells or testicular cells, and by simple manipulations getting them to revert to their stem cell status. Now, we've always thought that the cells that give rise to sperm, these testicular cells that this caller refers to are kind of close to stem cells. They're really part of our germ line. That's the cells in our body that are important for carrying on heredity, for passing on the species. So we always knew that they had this kind of immortality about them. But what's amazing about these testicular studies is that simply placing those cells in a Petri dish with a cocktail of growth factors actually gets them to revert to stem cells.

And I think this is really fascinating. It speaks for many, many breakthroughs in the years to come. We really do hope that this is going to give us new insights into biology and maybe teach us how to actually use cells to treat diseases in the future.

PALCA: Although it's - just thinking that - at one point, you were trying to get embryonic stem cells to turn into testicular precursors. Now they're talking about going the other direction.

Dr. DALEY: Well, you know, biology is a to and fro.

PALCA: Yeah.

Dr. DALEY: We're learning a lot about how to become more primitive and also how to become more specialized.

PALCA: Well, actually…

Dr. DALEY: I think we need both.

PALCA: I was going to throw that back to you as a sort of a final question. It feels a little bit like the nature of cells and what it means to be a particular cell is - I mean, what we understand, the nature of what it means to be a particular cell is undergoing a sort of a shift now?

Dr. DALEY: Yes, it is. I mean, I think we're astounded as biologists to think that we could take a cell that's been perhaps sitting in your skin for years and reawakened its embryonic potential. I mean, I think that's a really startling capacity for the cell. It really means that the genome is very plastic and that ultimately we hope to be able to turn that mutability, that versatility into clinical ends(ph).

PALCA: All right. Well, I'm afraid that's all we have the time. George Daley, thanks very much for spending time with us today.

Dr. DALEY: Thanks for having me, Joe.

PALCA: George Daley is an associate professor of biological chemistry and molecular pharmacology at Harvard Medical School, and an associate professor of pediatrics at Children's Hospital in Boston.

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