Stellar Lab Radio – Episode 1
Guest: Dr. Takanori Takebe
Creating organs from iPS cells—there is a researcher who continues to take on the challenge of making this vision of future medicine a reality.
In this inaugural episode of Stellar Lab Radio, we welcome Dr. Takanori Takebe, the world’s first scientist to develop a “mini liver” and a leading figure in organoid research.
Stellar Lab Radio is a talk series that shines a light on “world-changing research that no one knows yet.”
Top researchers at the forefront of their fields share the stories behind their cutting-edge science, breakthroughs, and visions for the future.
In the second half of the episode, Dr. Takebe discusses his discovery of mRNA transfer between mouse and human cells, his “phenomenon-first” approach to research, and the personal roots and philosophy that guide him as a scientist.
He also reveals groundbreaking findings that challenge conventional understanding of liver development.
Tune in to explore a new frontier in life sciences, seen through the eyes of those at the front lines of discovery.
🎧 Listen now on Spotify, Apple Podcast
The previous episode:
On New Challenges and Recent Research
Sean: This might be a bit of a shift in topic, but speaking of new directions—like venturing into completely different areas or taking on unconventional challenges—Dr. Takebe, if you’re able to share, I’d love to hear about anything recent you’re working on. Since your work on the “mini liver,” I imagine there have been various collaborations and research expanding in multiple directions. Is there anything you’ve been working on lately that you find especially unique, mysterious, or cutting-edge?
Takebe: Well, the most unusual project we’ve done recently might take a bit of explanation, but our lab often starts by mixing things that no one else has mixed before—without a specific intent. One of those projects involved trying to mix mouse and human cells.
Generally speaking, mouse and human cells don’t mix well. Because they’re different species, they naturally tend to cluster with their own kind. When we mix them, the mouse cells and the human cells form their own separate clusters—what we call colonies—and they end up forming these large circular shapes, completely segregated. It’s like there’s a repelling force between them.
But then something strange happened. After mixing the cells and separating them again—collecting mouse cells on one side and human cells on the other—we found that human genetic material was appearing in the mouse cells, and vice versa. More specifically, in the human cells, we detected messenger RNA (mRNA) originating from the mouse.
From a conventional cell biology perspective, that should be impossible. So the most likely explanation would be experimental contamination—maybe some mouse cells accidentally got into the human sample, or vice versa. That’s where most people would stop and write it off as an error.
But we’ve been observing this phenomenon for about seven years now, and it kept happening. We thought, maybe this isn’t just noise—so we kept pursuing it. The project originally started in Cincinnati. We considered the possibility of contamination very seriously, but even accounting for that, the amount of cross-species material was far too high. It seemed like actual information was being transferred.
We submitted the work to journals like Nature, but no one believed it.
Eventually, the researcher leading the project graduated and took a job in industry, which left us in a tough spot. Fortunately, one of our faculty members—who was at Tokyo Medical and Dental University at the time and has since moved to Osaka University—offered to continue the research. They greatly improved the experimental precision, and finally confirmed the phenomenon was real.
To explain more precisely: we found that genetic material from mouse cells—specifically, mRNA—was somehow penetrating human cells and being translated into functional proteins. In other words, mouse-derived information was being actively used inside human cells. We published this in a fairly prominent journal earlier this year.
Traditionally, the flow of genetic information follows a simple path: DNA → RNA → Protein. That was thought to be the only route. But what we found suggests that neighboring cells can strongly influence one another—potentially injecting harmful messages directly into surrounding cells and altering their nature. This was the first paper to propose such a phenomenon.
And when you think about it, it kind of makes sense, right? There’s a saying, “birds of a feather flock together.” People with similar personalities gather and influence each other. If you’re around rebellious types, the group feels a bit rebellious; if it’s more introverted people, the group becomes quieter. We found something similar might be happening with cells—that they’re deeply exchanging information with their neighbors.
If that’s true, it could totally change how we think about biology and disease. For example, maybe cancer cells aren’t bad on their own—they might be sending out bad messages to the surrounding environment. That’s why we reported this as a new phenomenon called mRNA transfer. But it was hard to get people to believe it. Even now, some scientists think we’re half-making it up. Personally, though, I think it’s one of the most exciting things we’ve studied.
The Possibility of mRNA Transfer in Cancer Research
Sean: Mice and humans are fundamentally different species, right? But if mRNA is being transferred even between them, wouldn’t it be even more likely to happen within a human body—like between one’s own cells, especially cancerous ones?
Takebe: Exactly. It could be happening quite frequently.
Sean: Do you see this becoming the basis for a next research project?
Takebe: Yes, that’s something I really want to pursue—especially in the context of cancer.
The only reason we were able to notice this phenomenon in the first place was because we mixed mouse and human cells. Their genetic codes differ just enough that we can tell which message comes from which species. For example, we can say, “This belongs to the mouse,” and “This one’s from the human.”
But when you’re looking at human-to-human cell interactions, proteins and messages are often so similar that they’re indistinguishable. There’s no way to separate them clearly, so nobody notices if something is being transferred. That’s probably been the major limitation in detecting this so far.
So right now, what we’re trying to do is develop tools that allow us to trace messages from specific cells. For instance, if something originates from cell A, it would carry a small label or tag, so that if it’s later found in cell B, we can confidently say it came from A. I think once we have that tool, we’ll be able to start clearly detecting these transfers.
Cancer research would be the next step after that.
Tool Development and the Role of Papers
Sean: I see. That actually brings up something I’ve been meaning to ask. In your research, you often seem to need to develop tools, and those tools themselves can be impactful—not just their creation, but how they’re applied.
So, in cases like this, would you end up publishing two separate papers—one on the tool and one on the findings? Or do you have to combine them, since a tool alone might not warrant a publication? How do you think about that?
Takebe: That really depends on the lab’s philosophy. In our lab, we take a “phenomenon-first” approach. So when we come across a curious phenomenon—something that can’t be explained, something biologically mysterious—that’s what we focus on. And if we need a tool to investigate it, we’ll create one. That’s how we operate.
But the trend these days is the opposite: tools first. You develop a new tool, and then find a novel application or field where it can be used. That’s become a huge trend. A good example is the Chan Zuckerberg Initiative—CZI. Their team works just like that.
They build tools to profile every single message in a single cell, and then explore what kind of questions can be asked using that data. That approach leads to interesting research, and I think that’s where the global research community is generally leaning now. There are a lot of tool developers out there.
But here’s the challenge: just building a tool doesn’t usually result in a high-impact paper. Journals like Cell, Nature, and Science—the top-tier ones—place the highest value on insights and discoveries. Tools are just means to uncover something. So what really gets evaluated is how interesting the thing you uncovered is.
That’s why a tool alone rarely leads to publication in a top journal.
So, even tool developers need to find truly compelling areas or phenomena where their tools can make a difference.
On the Chan Zuckerberg Initiative (CZI)
Sean: I see. So would it be accurate to say that an organization like the Chan Zuckerberg Initiative (CZI) isn’t necessarily focused on publishing a ton of papers, but rather on trying to cure all diseases—and that’s why they emphasize tool development?
Takebe: Hmm… That’s probably true in terms of the organization’s overarching mission.
But I don’t really get the sense that the individual researchers there are thinking about it quite that way. There’s often a big gap between grand visions like “curing all disease” and the grounded, day-to-day work we’re actually doing in research.
I think what happens more often is that researchers pursue their work, and over time it ends up aligning with the mission. But it’s not like they’re developing tools while constantly thinking, “I’m doing this to eliminate disease from the world.”
At least, that’s not the impression I get.
A “Phenomenon-First” Mindset
Sean: That’s fascinating. On the flip side, you mentioned a phenomenon-first approach…
Takebe: Exactly. And that, I think, is what makes biology and medicine so intriguing—because honestly, we still don’t understand most phenomena.
Why does this happen? What causes that? We just don’t know.
So I believe that one of the most important instincts a researcher can have is the ability to take a step toward those unexplained phenomena and throw a meaningful question at them.
It’s like… why did you, Sean, choose to wear that shirt today? Or why did the architect choose that size of glass for that window in this house?
Being able to spot those little oddities or curiosities in everyday life—and then turn them into questions—is such a valuable skill. Because interesting phenomena are everywhere. But most of the time, we just overlook them.
Even in our own lab meetings, people will present what they consider “negative data” and say, “Well, this wasn’t very interesting, here are the results.”
But I’ll say, “Wait, what if you looked at it this way? Isn’t that actually pretty intriguing?”
And they’ll admit they hadn’t thought of it like that.
So many times, it turns out that just being willing to reinterpret what you’re seeing changes everything.
But if you look at phenomena through a traditional lens—based on what’s already known or expected—you might not even see the phenomenon in the first place.
That’s why I think it’s important to cultivate a mindset that sees the world through curiosity. You need eyes that can pick up on those subtle, unexplained things happening all around us.
The Common Ground Between Design and Research
Sean: I see. So, it’s about never losing that sense of curiosity—but also, just asking “why” in the first place. That really reminds me of how designers think.
In fact, I always say that a designer’s favorite question usually starts with, “So… why is it even like this?” And I feel like that’s kind of similar.
Takebe: I think you’re absolutely right. That’s a really important kind of sensitivity to have.
Sean: It makes me wonder if your interest in communication design stems from that shared mindset. Is that something that draws you in?
Takebe: That’s an interesting point. To be honest, I didn’t have any connection to it originally. But recently, I’ve started to see it that way.
Maybe I’ve grown up a little. (laughs)
Roots and a Personal Encounter with Illness
Sean: I see. So what would you say your roots are?
Takebe: It’s a really personal story, but when I was around a kid, my dad had a stroke when he was about 39. It was pretty serious.
He’s still alive and doing well today, thankfully, but at the time, his condition was quite bad. He was a regular salaryman, but he was constantly overworked—going out drinking almost every night, coming home late, and then leaving the house by 6 a.m. His body was under a lot of stress. His blood pressure was something like 250. He was overweight and had high cholesterol and other issues.
We didn’t have any doctors in our family—and to be honest, my family doesn’t trust doctors.
Sean: And yet you ended up working in the field of medicine?
Takebe: (laughs) Well, technically, I didn’t become a doctor in the traditional sense!
Nobody in my family really trusted doctors. Even though my dad was prescribed medication, he didn’t take it seriously.
Looking back, it felt like the stroke was inevitable. That whole experience stuck with me for a long time. Then I got into med school. I studied fairly seriously for six years, but I came to this realization: no matter what department I joined or what method I used, I didn’t think I could have saved my dad.
Sure, I could have done something once the stroke happened. But if I wanted to do something before the stroke—prevent it—there were so many points where intervention could’ve made a difference: eating less, exercising, managing work stress, spending more time with family.
There were so many things that could have been done—but the kind of medicine we were being taught didn’t offer any tools to address those things. That really hit me hard.
So even as a student, I started wondering: What can we do to reach people before they get to that point?
And the first thing I tried was using media and advertising.
Using Media to Address Healthcare Issues—and Its Limits
Takebe: I tried using newspapers and TV. Back then, there were a lot of social issues being discussed—like how suicides were increasing due to Facebook, and so on. I believed that if we could create a movement through media, we might be able to change something.
And actually, it did work at first.
When I was a student, there were many healthcare-related social issues. One example was in obstetrics: there was a tragic case where a pregnant woman died because she couldn’t get admitted to a hospital in time.
She didn’t have a regular OB-GYN, and multiple hospitals turned her away—a situation that the media called being “passed around.” That incident became a major public issue in Japan at the time. I wanted to help solve problems like that.
So I used the media—TV, NHK, major newspapers—and managed to do some PR. We were able to create a bit of a movement.
But then, I realized: this would all fade in a month.
I felt a sense of defeat again.
At first, I was proud. I thought, Hey, I just did something no med school professor could do. But the momentum didn’t last. That’s when I realized—media alone isn’t the answer.
That led me to think that we need people who can continue these efforts creatively—through design, through storytelling. It’s not enough to just treat people after they get sick. We need professionals who can engage with people before and after they enter the healthcare system, at touchpoints throughout their daily lives.
And those professionals need to have at least some awareness of health and medicine.
While I was thinking about all this, my dad—who was 50 at the time—randomly spotted a call for proposals in the magazine R25, from advertising giants Dentsu and Hakuhodo. He said, “Hey, you’re always talking about creative design and stuff. Why don’t you give this a try?”
It was during national exam prep, and honestly I was bored, so I applied—and I got selected. That led to connections with all sorts of creators and designers. Ad agencies are full of people like that.
Once I realized how much could be done in that space, I got involved in different projects. Then around 2018, my alma mater’s med school in Yokohama suggested I start something. So we created a center—and that’s how I ended up where I am now.
So yeah, my roots are totally different from most.
Sean: I see. Your roots are totally different from mine, but the direction you’re aiming for, your perspective—it feels really aligned.
Takebe: Yeah, maybe the process is similar.
Like, finding areas no one’s tackled yet, and figuring out who to collaborate with to make it happen.
I think that approach—the way of putting things together—is actually quite similar.
What Are You Ultimately Aiming For?
Sean: I see. Listening to you talk about your research, your interest in design, and how your work is even crossing national borders—I can’t help but wonder:
What do you ultimately want to achieve?
Are all these paths converging toward a single vision? If so, what is it?
Takebe: Yeah, I get that a lot—and to be honest, my answer changes every time I’m asked.
For the past few years, I used to say that I wanted to realize something I called “My Medicine”—a world where every person could have their own personalized medicine. That was my vision, and I’d present my work as a multifaceted approach to achieving it.
But more recently, I’ve started to feel that wasn’t quite it.
These days, what drives me is simply doing what excites me—what makes me go “wow, this is interesting.”
And doing that in the best possible way, sharing it with the world in the most impactful way I can. That’s the motivation I’m running with now.
The truth is, times change, and what’s interesting also changes.
So committing myself to a fixed version of the future right now? That just doesn’t sit right with me anymore. I think organizations like GAFAM can do that sort of thing. There are people out there much better suited to building those kinds of futures.
Of course, I do want the world to improve in certain ways, and innovation is important—but I’m starting to realize that I’m probably not the one to lead that charge directly.
Instead, I want to keep observing the interesting phenomena that are happening around me, valuing them, and putting them out into the world in ways that make people go, “Whoa, that’s fascinating.”
So… yeah. I don’t have a single big vision, really.
Sean: But ultimately, it’s about why does this exist?, or what’s going on here? You want to discover those phenomena, explore them, and that curiosity becomes your motivation—it propels all the things you do.
Takebe: Exactly. That’s it.
A New Discovery in Liver Development
Takebe: One more thing—I’ve been working on liver research. Well, actually, I’ve always been working on it, haha.
The development and formation of organs have been studied for hundreds of years. Now that I think about it, I regret not bringing this up earlier when I was asked about my most interesting research. This is what I should have said:
We’ve made a discovery that actually challenges the textbook understanding of liver development.
The liver is such a mysterious organ. With organs like the pancreas or the brain, if you knock out a specific gene—completely delete it—you can entirely prevent that organ from forming. Like, no brain, no eyes, no heart, no lungs. That’s possible.
But not the liver.
You can’t eliminate it. No matter how many genes you knock out, the liver still shows up. That’s been a mystery for a long time.
What we discovered is that the liver doesn’t originate from just a single, defined population of cells. It actually comes from multiple cellular “families”.
For most organs, there’s usually one key cell type, and if you eliminate that, development stops entirely. But for the liver, there are multiple such key populations. So even if you shut down one pathway or eliminate one type, the others can compensate for it.
That’s why you can’t completely eliminate the liver via genetic engineering.
And that’s the discovery we’ve made. We’re actually submitting a paper on it next week.
Sean: That’s incredible.
Takebe: Pretty cool, right?
I mean, all those textbook diagrams—the ones used to teach med students and biology students—they’re not wrong, but they’re definitely incomplete. And even in this age where we feel like we can understand everything with advanced tools and knowledge, there are still things we fundamentally don’t know. That’s what makes biology and medicine so fascinating.
It’s wild to realize that for something as basic and central as the liver—something we deal with daily—we’re still in the dark about some of its most fundamental mechanisms. That’s why I find this work so exciting.
