Today, we’re going to learn all about stem cells with Naz. Right guys, welcome to another episode. Today, we’re here with Nazli Eskici, right? Eskici? Eskici. Eskici! I’ve already murdered the name, that’s the way to start. She is a friend of Giuliano and she is a scientist. She is a Ph.D. student working in disease modeling using stem cells at the University of Helsinki. We thought it would be interesting to have somebody who’s from the field, to learn more about stem cells from somebody who works with them so that, eventually, when we have episodes about the role of stem cells in aging, we’ll be prepared. Before we dive into the science questions, can you tell us exactly what is the field that you’re studying? What exactly you are doing for your Ph.D. For my Ph.D., we are working on mostly developmental disorders which affect human growth and development. We are trying to understand the mechanisms of diseases, so we’re using stem cells. What brought you to this particular field of research? Life? Sorry.
“As a little girl…” I don’t know. I cannot give an exact answer for that, but I was always curious about how the human body functions and how diseases disrupt this function, and how diseases happen, what are the mechanisms, so I started to… I had my major in biology, and then I had a Master’s degree and then a Ph.D. and happened to be here, and stem cells are creating so much potential to work on. Absolutely. I suppose, probably, the interest in this particular sub-field came after you got your biology degree or maybe something you had even before that you were already interested in clearing out diseases. I don’t know, even as a kid, I was curious, I had all the books for children explaining… About stem cells.
Not stem cells. But the human body and diseases and those kinds of things. Did you have a phase when you were thinking about becoming a doctor? Yes. I was thinking that it definitely sounded like it. You first decided to become a doctor, and then you were just more interested in actually Biology, not vanity.
Figuring out how that happens. Other than curing them, yeah. Exactly. Unlike me, I wanted to become a physician, then I switched to biology because I didn’t get into med school. Oh, sorry, very different for you, actually.
Womp womp womp womp… So, you mentioned stem cells, and can you explain to us in layman terms what they are? Stem cells are the cells which have the ability of making all of the specialized cells in the human body. That means they have the capacity to differentiate into all the cells we have in the body. So they can become other types.
Yes. That’s the point. They’re like blank slates. Tabula rasas. Posh reference. Wow. That was so smart. I get science. I understand that they, besides being able to differentiate, becoming different types of cells, more specialized, more particular to certain types of tissues, like heart, muscle, or whatever, they also, can go on reproducing, in principle, indefinitely, unlike other cells, which have kind of a hard limit. Yes, that is all true, especially for embryonic stem cells. Is there some kind of hierarchy? Embryonic stem cells can divide a lot, and then there are stem cells that can divide a lot but not that much? Yes, pretty much something like that, but embryonic stem cells can divide indefinitely. They have the potential to procreate indefinitely. There’s no limit at all?
No. For embryonic stem cells.
Those are some lucky cells. I want some of those. Do I have them? Where do I have them? Well, you had them. Oh no, I lost them. When you were an embryo. So we have no stem cells in our body as adults? No, we have. Not the embryonic. That makes sense, not the embryonic ones if you’re not an embryo anymore. You’re going to lose your job doing the trivia. I’m going to lose it now. Hi boss! That connects to another point, I would say, because if you say that the embryonic stem cells can reproduce forever, so to speak, then it kind of connects to what pop science says about stem cells, that they are immortal. Can you clarify? “mmorta” is a terrible word because it is misinterpreted. Yeah, exactly. “Immortal” is not the right word, probably, but they have the indefinite capacity of dividing, so that makes them “immortal”. Maybe I can say that they just don’t age like other cells, they don’t go to cellular senescence. The replicative senescence, they don’t have because they have telomerase, so they maintain their telomeres. They can divide indefinitely, so that means that yes, they’re “immortal”. That’s actually a point that we can expand on, because, again, we have new terms: we have telomerase, and we have telomeres. What is a telomere? Older cells, like somatic cells, in our body, which are body cells, have telomeres that are shortened gradually as they are dividing. So, they are basically the edges of the chromosome. I don’t grow them; on each dividing, they keep shortening. At some point, they have a limit, and it’s called replicative senescence. It leads that cell to die. When they get too short, basically. When the telomeres run out, that’s when they become senescent cells, do I understand correctly? Yes, it’s a process of replicative senescence. Then they stop dividing and kill themselves. Basically.
Work done, time to go. That’s true for somatic cells; they have a hard limit they cannot overcome, whereas stem cells have a way around this problem, which is the fact that they have telomerase. What is that, exactly? Telomerase is an enzyme that maintains telomere length, and it protects them from shortening. So they get rebuilt? After each cycle, they just rebuild it? Basically. This is something that only the stem cells possess. I’m not comfortable with saying “only” because I’m sure there’s an exception. Probably, yeah. Probably so. I’m not comfortable with saying “only”.
Biology’s made “only”. Of exceptions, exactly. If I have learned anything since I’ve been in this business, it’s that, basically, the biology book is a book of exceptions. Not a book of rules. Yeah, exactly. There’s an exception for everything. All stem cells express telomerase? I can say neither yes nor no to that question. But yes, embryonic stem cells do express telomerase, but we also have adult stem cells in our body. Right now, we all have them in different tissue. Even Veera? Even me.
Even her. Well done. Regardless of their dividing capacity, they have low or absent telomere activity. Comparing.
I did not know that. That actually comes as a surprise to me as well; I thought that they at least had… But they don’t divide as much as embryonic stem cells or some somatic cells in our body, they basically stay dormant unless they are needed to divide. If I understand you correctly, that means that those stem cells eventually will run out of steam even though they can replicate indefinitely? If they don’t have any telomerase, their telomeres are going to run out one day as they are called to replicate? To be honest, I’m not exactly sure either. I just know that they have really low activity, even absent sometimes. But they have proliferative capacity, so they can make more stem cells, in case of injury for example. Such as muscle stem cells. That makes sense. After they divide, when the body needs them at one point, probably during aging or time, they would just become quiescent, senescent, basically. Probably, yeah. Which would be connected to the stem cell hallmark, stem cell ablation. We’re going to get there. It’s hard to say at this point if the hallmark, the stem cell exhaustion hallmark, will be out before or after this video, wer’re nowhere near… We’re going to see what happens. We’ll be able to make predictions, but stay tuned, there will be an episode at a point in time. Wow.
I know, Veera, very precise. Hopefully in our lifespan. Yeah, hopefully, that’s what we’re working on. By the way, this is something that got me puzzled for a while, I came up with this question, so you can blame me in case you don’t like it. I’ve always been confused for quite some time whether stem cells are the only cells in the body who actually are called to divide when necessary, or if somatic cells, cells that have already been specialized and have gone as far as they could as I understand, if they can divide too. It depends on the cell type. But yes, of course, our somatic cells are dividing. By each division, their telomeres get shorter and then they… So basically…
Senescent. But there are exceptions. Of course there are, I know.
Like differentiated neurons. They don’t divide anymore. The other somatic cells, yes.
They can. Which makes sense, I was actually browsing Wikipedia at a point some few days ago, and I was having a look at the hierarchy, I didn’t know that there was an entire hierarchy of multipotent and pluripotent, sometimes I did know, but I didn’t know the entire hierarchy. Somatic cells can only make copies of themselves. Yeah, exactly, which is called mitosis. They only give rise to daughter cells which are the same. That’s not differentiation.
Yeah, no. It’s just replication.
Replication. Not replication, but division. Procreating. Whereas, basically, when you have, again, this is my guess based on what we have discussed thus far, when you have a stem cell of some kind that is capable of making different types of cells, basically, it will split into a smaller version of itself and then a more specialized cell? Would you say, guys? Embryonic stem cells are pluripotent, which means they can make all the types of cells in the body. When they divide, they also have self renewal capacity. They can either divide and make two new stem cells, or they can differentiate, or they can divide and make one stem cell and one cell which is primed to be differentiated. All right, so that differentiation will happen later on. Yeah, basically. Like a progenitor or something? Yeah, yeah.
Of the specialized cell. You brought this on yourself: What is a progenitor? Is that an English word? It is. It’s a scientific English word.
I was basically.. ah, okay. It’s a cell that will then give rise to a specific, specialized cell line. A progenitor of neuronal cells, for example, will only generate future neurons, basically. Is that kind of an in-between state?
They are kind of… also stem cells, I mean not stem cells, but they are… neural stem cells, yeah, it’s the neural stem cells. They are multipotent. Not pluripotent anymore; they can only make neurons. But they are not neurons yet. So it’s some kind of in-between state between the stem cell that generated it and the cell that they’re going to specialize in, as I understand it. It looks like, sounds like, the progenitor is in between the stem cell that created it, that created the progenitor, and the cell that it’s going to be. It’s neither of those.
I guess we could say that, yeah, sure. I’m just really happy that we got the answer “in between” here, because I was about to ask, what is the difference between pluri-
Pluripotent. and multi-, but then you answered, pluri- can become basically anything, and multi- can become multiple things, like the name says, but in a specific line. Yeah, exactly, for example, hematopoietic stem cells are multipotent, they can only give rise to blood cells or hematopoietic stem cells. Basically, I think the best way to envision this is to imagine a tree-like structure that starts from a root: there’s just one thing, and then it splits into more things and then the root of each branch only can branch into specific sub-branches. As you go down the tree, you basically run into specialization, and there’s only one thing you can do when you do that when you get to the bottom, which is the somatic cells. Cool beans. I think we covered that. I actually got educated. I actually wanted one of those things.
What, stem cells? Yeah. I keep them in a jar. A tree root?
They are, though. I’m sure they are. I’ve never seen one live. No, I wanted a chart of the hierarchy of cells and stem cells in particular. I wonder if there is a complete one, probably not, I’m guessing that there is something around the corner that we still don’t know about. I’m pretty sure, in specific tissues, you can find on Google a specialization tree, for example, from progenitors down to..
I want something to hang on my wall. That was extremely interesting.
Yeah, really interesting. You were saying at the very beginning that you use stem cells in your research in order to model diseases and figure out how they work and maybe treat them, hopefully; that’s the whole point. What diseases are you trying to model, specifically? We are mostly working on the diseases which are affecting human growth and development, and one of them is Kallmann syndrome, which is a genetic disease and really Kallmann in women. What does it do, exactly? It’s caused by a deficiency of a specific neuron type in the brain, and it causes developmental delay, infertility, lack of or delayed puberty in both men and women, it’s a growth-related syndrome. How exactly do stem cells play a part in modeling this disease? We are using stem cells as a tool. I’m not working on stem cells, I’m working with stem cells. Because they have so much potential in every field, we are just using them as a tool and differentiating them into relevant cell types for the disease which we are working on. So you’re using them to make the cells that you need.
Yes. That’s so clever. That’s so smart, that the human body has something that we can just take and say “Now become this. I need this.” Are you thinking that it’s easy? As a non-scientist here, that’s basically how I understood it. You take some cells, you tell them “Change”, and they do it. And you look at them really, really intensely and they die. They’re so fragile that even if you just look at them badly… I don’t work with stem cells myself, but apart from you, I also know other people who work with stem cells, and everybody hates them, because they’re so fragile, that if you fart in the room, they die. I’m joking, but well…
They can. That happens to people as well, depending on the circumstances. Yes. But they’re really annoying. All the stem cell scientists I know have a love/hate relationship with the stem cells. Because they’re so cool, like they’re really so cool, that it’s impossible not to love them, but it’s really difficult to work with them, so you hate them, but I sometimes feel like I have a kid. Because they require constant attention. I’m going to go to the lab when I leave here. You have to go over there and cuddle them and hug them? Okay. Nice that you thought they were kids because from the way you were describing them, I just think about really talented Hollywood actors that are also total d–ks, you’re just like “Here’s your coffee” and they’re like “No, I wanted a mocha.” You never know what they want to do. You were talking about how you divide the stem cells or turn them into something different. Differentiate. Nice, I can pronounce stuff. Anyway, how do you do it? You said that it’s very difficult because they’re… mean people who like mochas instead of coffees? How do you, then, do whatt you do? There are many differentiation protocols for each subtype, but, basically, they’re trying to mimic what happens in the human body. While they are differentiating, they do that using the signals from the environment, while we are trying to mimic those signals using signaling pathways, inducing them or inhibiting them to direct them to the right direction that we want. Tell me if I’ve got it right: You use chemicals that resemble the chemicals that they would receive in the human body. Yes, small molecules, chemicals, proteins, recombinant proteins. That you give them artificially, because you don’t have the rest of the body around. Yeah, exactly that. They’re in the dish, so we’re just putting it into their media. So you’re not actually fooling them, you’re actually giving them exactly the same chemicals that they would receive in the body to turn into neurons. I wouldn’t say exactly.
Well yeah, similar. But they’re trying to mimic the processes. The stem cells that you’re using as a tool, you’re trying to make the type of cells that are deficient in the disease that you’re modeling. You’re doing that in order to learn something about those cells and find out why they end up lacking in those patients? Yeah, basically, because we are not sure how the disease happens, exactly. We know there’s a defect in those cells, but we don’t know if the problem is about their formation, their migration, or their function. It’s not necessarily so that the patients don’t have them, it might be that they have them and they don’t work very well. Exactly, or they have them but they are not in the right position they need to be in because they cannot migrate properly or they don’t function correctly in the place, or they may be lowered in number. Because the thing is, regarding migration, is that there are specific niches in the brain; only a couple of places in the brain create new neurons, so those neurons have to migrate where they need to be, and these cells might be lacking the tools to go in position. That’s why they need to migrate. The human body is so friggin’ fragile. It’s so cool, but then you hear about these tiny, on the cell level, we’re talking about tiny inconsistencies, there’s something that goes just a bit wrong, and suddenly we have a full-on disease. It’s not very likely that it will happen, but when it does happen, you’ll have real trouble trying to fix it, because it never came with blueprints or an instruction manual. It’s an entire reverse engineering problem with no instructions whatsoever. But I would imagine that it’s quite challenging trying to figure out which of the three options it is. At the same time, how do we know in the first place that the problem lies within these cells if we’re not sure which of the three options it is? I’m not questioning the data, I just can’t figure out how they figured out that this is the issue. One of the reasons is, for example, those cells are born in the olfactory bulb, which is the nose area, and some of the patients lack olfactory bulbs completely. I was curious to ask if there are, besides this disease that you mentioned, there are others that you work on or is this your specific target? Mostly Kallmann syndrome, but Kallmann syndrome consists of other things, one of them is another disease, which is congenital hypogonadotropic hypogonadism. Can you say that again three times faster? I’m really surprised I was able to say that once. What is that? A tongue twister.
That is the disease that originates from a lack of adult neurons and results in growth retardation, infertility, and other growth defects. But if it comes along with a lack of sense of smell or a reduced sense of smell, then it is termed as Kallmann syndrome. Okay, so that’s the difference between them.
Yeah. There is some similarity between them, I understand. Yeah. Kallmann syndrome is congenital hypogonadotropic hypogonadism plus a lack of reduced sense of smell. Thank you very much for joining us today. Good luck with your research.
Thank you for having me. Maybe one day we’ll have you again, we’ll have updates about your research, who knows. It’s been very nice to have you, it’s been very fun, very interesting, and again, thanks. Thank you very much, and thank you to all of you who watch this video until the end, you’re true troopers, and if you have any questions or anything you want to tell us about this episode, your opinions, your experiences, please comment down below, and if you want to see any future videos, subscribe, like this video, and we’ll see you next time. Bye.