A Mouse With Two Dads — and a New Frontier for Biology | Katsuhiko Hayashi | TED

翻译人员: Lening Xu 校对人员: Manlin Fang

It is my great pleasure to be here

很高兴来到这里，

to share some news from biology today with you.

和大家分享生物界的消息。

So your life and mine starts with this.

我们的生命源于——

The union of sperm and egg.

精子和卵子的结合。

The fertilization involves sperm from the father

受精需要父亲的精子

and egg from the mother.

和母亲的卵子。

They meet in the usual way,

它们以通常的方式相遇，

and the fertilized egg acquires the potential

受精卵获得了产生 像你我这样的个体的潜力。

to give rise to the individuals like you and me.

If you trace back your generations, you are derived from your parents,

如果向上追溯， 你是父母生出来的。

and your parents are derived from your grandparents,

你的父母是你的祖父母们生出来的，

and so on, in distant past.

如此这般，直至至遥远的过去。

This perpetuity can only be achieved

这种永续只能通过

through what biologists like me call germ cell lineage.

像我这样的生物学家 所说的生殖细胞谱系来实现。

These are the only cells that are immortal

这些是你体内 200 多种细胞中 唯一永生的细胞。

among more than 200 types of cells in your body.

The rest die with you.

其余细胞在你体内死亡。

So these immortal germs, called gametes,

这些永生的生殖细胞，称为配子，

are very important,

非常重要，

and we call them germline.

我们称之为生殖系。

In our society, this unbroken line is under threat.

当今社会，这条不间断的线正受到威胁。

The present generations are having children later and later,

当代人生育的年龄越来越大，

and the older germ cells are less likely to result in successful fertilization,

较老的生殖细胞受精成功率较小，

which leads to the declining birth rate.

导致出生率下降。

It's not just the people.

不仅人类是这样。

The continuous decrease in the reproductive rate

大牲畜繁殖率的持续下降

of large livestock

has resulted in huge economic losses.

造成了巨大的经济损失。

Setting aside the human needs,

撇开人类的需求不谈，

there are endangered animals down to a few individuals.

濒危动物只剩下极少数。

How can we preserve them?

我们如何保护它们？

That is where the assisted reproductive technology offers hope.

这就是辅助生殖技术所带来的希望。

Since Robert Edwards successfully combined human germ cells in a dish,

自从罗伯特·爱德华兹在培养皿中 成功结合人类生殖细胞以来，

more than 20 million babies have been born

超过 2,000 万婴儿通过这种

through this technology called in vitro fertilization.

体外受精技术出生。

However, current assisted reproductive technology

然而，当今的辅助生殖技术

can only be applied if sperm and egg can be obtained from the body.

仅适用于从体内获取的精子和卵子。

If not, there are no options available.

除此之外，别无他法。

But I would ask now:

但我想问：

Can we create germ cells in a dish?

我们能否通过器皿培养生殖细胞？

So this is a question.

这是一个问题。

So let's start with how the germ cells form in the body.

让我们从生殖细胞在体内的形成方式开始。

After fertilization, a fertilized egg undergoes cell divisions

受精后，受精卵经过细胞分裂，

and differentiates into the different cell types.

并分化为不同的细胞类型。

As it further develops,

随着它的进一步发育，

original cells, or eventual sperm and egg,

原始细胞，或最终的精子和卵子，

known as the primordial germ cells, emerge.

被称为原始生殖细胞，出现了。

These primordial germ cells then differentiate into the primary egg,

这些原始生殖细胞分化成雌性的初级卵子，

known as the oocyte, in the female,

即卵母细胞，

or spermatogonia, the precursor of the sperm in the male.

或雄性精子的前体精原细胞。

These egg and sperm mature over time,

这些卵子和精子随着时间的推移而成熟，

which is associated with the sexual maturation of individuals.

这与个体的性成熟有关。

Now imagine

现在，想象一下，

if this entire process were to occur outside the body.

如果整个过程发生在体外。

So my team and I have been focusing

因此我和我的团队一直专注于

on duplicating this entire process in a dish,

在培养皿中复制整个过程，

known as in vitro gametogenesis.

即体外配子发生（IVG）。

The key to generating the germ cells in a dish

在培养皿中产生生殖细胞的关键

is a type of cells called pluripotent stem cells,

是一种称为多能干细胞的细胞，

because they each have the ability to differentiate

因其能分化成

into any cell type in the body.

任何一种体细胞。

Martin Evans showed that such a pluripotent stem cell

马丁-埃文斯（Martin Evans） 证明了这种多能干细胞

could be derived from preimplantation embryo in mice,

可以来源于小鼠的植入前胚胎，

and James Thomson showed it could be done in humans.

詹姆斯·汤姆森（James Thomson） 证明了它也能来源于人体。

Based on these breakthroughs,

基于这些突破，

Shinya Yamanaka showed that any kind of cell in the body

山中伸弥（Shinya Yamanaka） 证明了任意一种体细胞

could be turned into the pluripotent stem cells

只需一组特定的蛋白质表达， 就可以逆转为多能干细胞。

simply by expressing a specific set of proteins.

These are called induced pluripotent stem cells,

这些被称为诱导多能干细胞，

and they possess the same potential as those derived from embryos.

它们具有与胚胎相同的潜力。

By using these pluripotent stem cells, we can hijack the germline.

通过这些多能干细胞， 我们可以干预生殖体系。

During normal development,

在正常发育过程中，

cells receive a signal that guides their differentiation

细胞会收到一个信号，

into the different cell types.

引导它们分化为不同的细胞类型。

By mimicking the right signals,

通过模仿正确的信号，

pluripotent stem cells can be directed along the pathway

多能干细胞能被引导

to differentiate into the egg and sperm.

分化为卵子和精子。

This has been successfully demonstrated in our laboratory

这已在我们的实验室中通过使用 小鼠多能干细胞成功证明。

by using mouse pluripotent stem cells.

By providing appropriate signals,

通过提供适当的信号，

we were able to generate mature eggs

我们能从大多数多能干细胞 产生成熟的卵子。

from most pluripotent stem cells.

Also to achieve this,

为实现这一点，

we created a mini ovary from pluripotent stem cells,

我们用多能干细胞创造了一个迷你卵巢，

allowing the oocyte to mature outside the body.

使卵母细胞在体外成熟。

Importantly, eggs produced in a dish are capable of fertilization

重要的是，培养皿中产生的卵子能够受精

and giving rise to yet more mice like these.

并产生更多这样的小鼠。

These looks the same as any other mice.

它们看起来与其他小鼠一模一样。

They grow up, they eat the food, they breed and live long.

它们长大，进食，繁殖，活得很长。

But in this case, the genetic mother of these mice

但这种情况下，这些小鼠的遗传母亲

is the pluripotent stem cell grown in a dish.

是培养皿中的多能干细胞。

With this in vitro gametogenesis,

通过这种体外配子发生，

the process of creating an egg requires only skin cells

产生卵子的过程只需要表皮细胞

or other easily collectable cells from the body, even cells in urine.

或其它易获取的体细胞， 甚至尿液中的细胞。

So this means actually this kind of technology can be applied

这意味着这种技术实际可以应用于

to the various mammalian species,

不同的哺乳动物，

including humans, livestock or even endangered animals.

包括人类，牲畜甚至濒危动物。

Several research groups have successfully produced

好几个研究团队已成功

the primordial germ cells from pluripotent stem cells

从多能干细胞中产生了原始生殖细胞，

in all these cases.

涵盖了上述所有种类。

Notably, our laboratory is actively involved

值得注意的是，我们的实验室积极参与了

in the repopulation effort for the northern white rhinoceros.

北方白犀牛的繁殖工作。

Sadly, there are only two females who remain on this planet.

难过的是，这个星球上仅幸存两头雌犀牛。

We have generated the egg precursors

我们已经从北方白犀牛的诱导多能干细胞 产生了卵子前体，

from the northern white rhinoceros induced pluripotent stem cells,

and are currently creating a mini ovary system

现在正在建造迷你卵巢，

to mature these precursors into the eggs.

使卵子前体发育成卵子。

But we can go further than [that].

但我们能走得更远。

By using this technology, we can skip the sex-dependent reproduction.

通过使用这项技术， 我们可以跳过依赖性别的繁殖。

Today, germ cells have different shape and different function based on the sex.

如今，生殖细胞基于性别具有 不同的形状和不同的功能。

This difference is genetically made by the sex chromosome.

这种差异是由性染色体在遗传上造成的。

In the human, males have an X and Y chromosome,

对于人类，男性具有X和Y染色体，

and the females have two X chromosomes.

女性具有两对X染色体。

From a genetic viewpoint,

从遗传学的角度来看，

this is the only difference between male and female.

这是男性和女性唯一的不同。

But in a dish, we can eliminate this difference.

但在培养皿中，我们可以消除这种差异。

So our laboratory succeeded in the switching from the XY chromosome

因此，我们的实验室成功地将XY染色体

to the X chromosome.

转换为X染色体。

How did we do that?

我们怎么做的？

Well, we took the skin cells from the male mice,

我们从雄鼠中获取表皮细胞，

and then made induced pluripotent stem cells,

培养具备X和Y染色体的诱导多能干细胞，

which have X and Y chromosomes, of course.

Then we made a lot of these cells.

然后我们产生了很多细胞。

In some rare populations,

在一些罕见的群体中，

unequal segregation of sex chromosomes occurs during cell division,

性染色体在细胞分裂过程中 发生不平等分离，

which means some XY chromosomes become one X chromosome

这意味着XY染色体变成X染色体，

that then doubles and becomes two X chromosomes.

再变成两条X染色体。

We picked that very rare population

我们选取这些有两对X染色体的罕见群体，

of these cells that have two X chromosomes,

and we made an egg.

我们产出卵子。

The egg derived from sex-converted induced pluripotent stem cells

来自性转换诱导多能干细胞的卵子的行为

behaves exactly [like an] egg from traditional females.

与传统雌性的卵子完全相同。

We then fertilized the sex-converted egg

然后，我们用精子使变性卵子受精，

with the sperm,

and this gave rise to typical healthy mice like these.

这就产生了像这样的典型健康小鼠。

They grow up, they eat the food, they mate and live long,

它们长大，进食，交配，活得很长，

just like conventionally bred mice.

就像传统饲养的小鼠一样。

The only difference is these are derived from two dads.

唯一的区别是它们源于两只雄鼠。

Looking at the history of reproductive technology like this,

纵观生殖技术的历史，

technologies developed in experimental animals like this

在这样的实验动物身上开发的技术

can eventually be applied to the human and other animals.

最终可以应用于人类和其他动物。

Today, the production of egg in a dish, even from traditional male cells,

如今，在培养皿中生产卵子， 甚至是从传统的雄性细胞中，

open a new possibility for reproduction in the future.

为未来的繁殖开辟了新的可能性。

We can create germ cells in a dish,

我们能再培养皿中创造生殖细胞，

and they can come from two fathers, two mothers

它们可能来自两个父亲、两个母亲

or perhaps other combinations.

或其他可能得组合。

Thank you.

谢谢大家！

(Applause)

（掌声）