TED Talks Daily - A mouse with two dads — and a new frontier for biology | Katsuhiko Hayashi

Episode Date: November 18, 2024

You're familiar with the story: a sperm and an egg meet to create an embryo, which has the potential to give rise to new life. But what if you could create a sperm or egg from any cell, even a single skin cell? Biologist Katsuhiko Hayashi discusses the science of in vitro gametogenesis (IVG) — an experimental technique for creating lab-made sperm or eggs out of just about any type of cell — and explores its implications for endangered species, human reproduction and more.

TED Audio Collective You're listening to TED Talks Daily, where we bring you new ideas to spark your curiosity every day. I'm your host, Elise Hwu. We are on the brink of a breakthrough in reproductive technology that could allow parents of the same sex to reproduce with DNA from both parents. That's right. But this kind of science wouldn't just help same-sex couples. As biologist Katsuhiko Hayashi presented in 2024, it could also keep biodiversity from extinction. He explains after the break.

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or your favorite podcast platform. And now, our TED Talk of the Day. It is my great pleasure to be here to share some news from biology today with you. So your life and mine start with this. The union of sperm and egg. The fertilization involves sperm from the father and egg from the mother. They meet in the usual way and fertilize the egg, acquire the potential to give rise to the individuals,

like you and me. If you trace back your generation, you are derived from your parents, and your parents are derived from your grandparents and so on, in distant past. This perpetuity can only be achieved through what biologists like me call germ cell lineage. These are the only cells that are immortal

among more than 200 types of cells in your body. The less die with you. So these immortal germ cells called gametes are very important. And we call them germline. In our society, this unbroken line is under threat. very important, and we call them germline. In our society, this unbroken line is under threat. The present generations are having children later and later, and older germ cells are less likely to result in successful fertilization,

which leads to the declining birthrate. It's not just people. Continuous decrease in the reproductive rate of large livestock has resulted in huge economic losses. Setting aside human needs, there are endangered animals down to a few individuals. How can we preserve them? That is where the assistive reproductive technology offered hope.

Since Robert Edwards successfully combined human germ cells in the dish, more than 12 million babies have been born through this technology called in vitro fertilization. However, current assistive reproductive technology can only be applied if sperm and egg can be obtained from the body. If not, there are no options available. But I would ask now, can we create a germ cell in the dish? So this is the question.

So let's start with how the germ cell are formed in the body. After fertilization, fertilized egg undergoes cell division and differentiates into into different cell types. As it further develops, original cells or eventual sperm and egg, known as the primordial germ cell, emerge. Then these primordial germ cells then differentiate into the primary egg,

known as the oocyte in the female, or sperm antagonia, the precursor of sperm in the male. These england spermatogonia, the precursor of sperm in the male. These england sperm mature over time, which is associated with the sexual maturation of individuals. Now imagine if this entire process were to occur outside the body. So my team and I have been focusing on replicating this entire process in the dish, known as in vitro gamma genesis.

The key to generating the germ cell in the dish is a type of cells called puripotent stem cells, because they each have an ability to differentiate into any cell type in the body. Martin Evans showed that such a puripotent stem cell could be derived from a preimplantation embryo in mice, and James Thompson showed it could be done in humans. Based on these breakthroughs, Shinya Yamanaka showed that any kind of cell in the body could be turned into the puripotent stem cells simply by expressing a specific set of proteins.

These are called induced puripotent stem cells, and they possess the same potential as those derived from embryos. By using these puripotent stem cells, we can hijack the germline. During normal development, cells receive the signal that guides their differentiation into the different cell types. By mimicking right signals, puripotent stem cells can be directed along the pathway to differentiate into the egg and sperm.

This has been studied in the study of the egg and sperm, cell type. By mimicking light signals, puripotent stem cells can be directed along the pathway to differentiate into the egg and sperm. This has been successfully demonstrated in our laboratory by using mouse puripotent stem cells. By providing appropriate signals, we were able to generate a mature egg from mouse puripotent stem cells. Also, to achieve this, we created a mini-overly from pilloportin stem cells,

allowing the oocyte to mature outside the body. Importantly, egg-producing dishes are capable of the fertilization and giving rise to yet more mice. These look the same as any other mice. They grow up, they eat the food, they breed and regrow. But in this case, the genetic mother of these mice is the puripotent stem that grows in the dish. And now, back to the episode.

With this in-vitogamy genesis, the process of creating an egg requires only skin cells or other easily collectible cells from the body, even cells in the urine. So this means actually this kind of technology can be applied to the various mammalian species, including humans, livestock or even endangered animals. Several research groups have successfully produced the primordial germ cells from pluripotent stem cells in all these cases. Notably, our laboratory is actively involved in the depopulation effort for the northern white rhinoceros. Sadly, there are only two females who remain on this planet.

We have generated egg precursors from the northern white line nacelles in these pilpotent stem cells, and are currently creating a mini ovary system to mature these precursors into the eggs. But we can go further than that. By using this technology, we can skip the sex-dependent reproduction. Today, jam cells have different shapes and different functions

based on the sex. This difference is genetically made by the sex chromosome. In the human, males have an X and Y chromosome, and females have two X chromosomes. From a genetic viewpoint, this is the only difference between the male and the female. But in a dish, we can eliminate this difference. So our laboratory succeeded in switching from the XY chromosome

to the XX chromosome. How did we do that? Well, we took the skin cells from the male mice and made an induced pylpotent stem cell, which have X and Y chromosomes, of course. Then we made a lot of these cells. In some rare populations, an unequal segregation of sex chromosomes occurs during cell division, which means some XY chromosomes become one X chromosome,

that then double and become two X chromosomes. We picked up a very rare population of these cells that have a two X chromosomes, and we made an egg. The egg derived from sex-combated induced bupoten stem cells behaves exactly like the egg from traditional females. We then fertilize the sex-combated egg with the sperm, and this gives rise to typical, healthy mice.

They grow up, they eat the food, they this gives rise to typical, healthy mice. They grow up, they eat the food, they mate and live long, just like conventional bread mice. The only difference is these are derived from two darts. Looking at the history of reproductive technology like this, technologies developed in the experimental animal like this can eventually be applied to the human and other animals. Today, the production of eggs in the dish,

even from traditional male cells, opens a new possibility for reproduction in the future. We can create a germ cell in the dish, and they can come from two fathers, two mothers, or perhaps other combinations. Thank you. Support for this show comes from Airbnb. If you know me, you know I love staying in Airbnbs when I travel. They make my family feel most at home when we're away from home. As we settled down at our AirBnB during a recent vacation to Palm Springs, I pictured my own home sitting empty.

Wouldn't it be smart and better put to use welcoming a family like mine by hosting it on AirBnB? It feels like the practical thing to do, and with the extra income I could save up for renovations to make the space even more inviting for ourselves and for future guests. Your home might be worth more than you think. Find out how much at airbnb.ca slash host. That was Kazuhiko Hayashi speaking at TED 2024.

If you're curious about Ted's curation, find out more at TED.com slash curation guidelines. And that's it for today. TED Talks Daily is part of the TED Audio Collective. This episode was produced and edited by our team, Martha Estefanos, Oliver Friedman, Brian Green, Autumn Thompson and Alejandra Salazar. It was mixed by Christopher Faisy-Bogan. Additional support from Emma Taubner and Daniela Ballarezzo. I'm Elise Hugh. I'll be back tomorrow with a fresh idea for your

feet. Thanks for listening. PRX