The researchers began with 132 embryos of the crab-eating macaque. Six days after fertilisation these were injected with human extended pluripotent stem cells, which can develop into any other cell type found in the body. Tagging the human cells with fluorescent markers allowed the researchers to track where in the developing embryo they, and their descendants, went.
研究人员从食蟹猕猴的132个胚胎着手。在受精后的第六天向它们注射人类扩展多能干细胞(EPSC)。这些干细胞可以发育成嵌合体内的任何其他细胞类型。用荧光标记物标记人类细胞,研究人员就能够追踪这些细胞及其后代在发育的胚胎中的位置。
In the early stages of development, mammal embryos develop into four distinct cell types. Epiblasts go on to form the organism itself; hypoblasts develop into the yolk sac; trophectoderms become the placenta and extra-embryonic mesenchyme cells make a membrane that surrounds the embryo. The chimera's human cells made their way into all four types of tissue, though they were outnumbered in every case. No more than 7% of the epiblast was made up of human cells, and just 5% of the hypoblast (in other areas the numbers were lower still).
在发育的早期,哺乳动物的胚胎会形成四种不同的细胞类型。外胚层继续形成生物体本身;内胚层发育成卵黄囊;滋胚层变成胎盘;胚外间充质细胞形成包裹胚胎的膜。嵌合体中的人类细胞参与生成了所有四类组织,尽管在每一类中的数量都少于猴子细胞。人类细胞在外胚层中的占比不超过7%,在内胚层只有5%(在另两类中占比还要少)。
Joint venture
大胆接合
The cells' location seemed to influence which proteins they produced. Human cells in the chimera's epiblast behaved more like those found in human embryos than those found in monkey embryos. But that was not true of human hypoblast or extra-embryonic mesenchyme cells, both of which behaved more like monkey cells.
细胞所在的位置似乎会影响它们生成何种蛋白质。嵌合体外胚层中的人类细胞的行为更近似于人类胚胎细胞,而不像猴子胚胎细胞。但内胚层或胚外间充质细胞中的人类细胞的行为却都更像猴子细胞。
The monkey cells, in turn, were affected by the presence of the human ones. The researchers found 126 different sorts of cellto-cell interactions among monkey cells in the chimeric embryos, compared with just 19 in non-chimeric ones, as well as differences in the activity levels of many genes.
反过来,猴子细胞也受到了人类细胞存在的影响。研究人员发现,嵌合胚胎中的猴子细胞之间有126种不同类型的细胞间相互作用,而在非嵌合体中只有19种。此外许多基因的活性水平也存在差异。
The cells were grown in a lab, which imposed limitations. The number of surviving embryos began falling by day 15. By day 20 none was left. But that was enough time for a process called gastrulation to take place. Gastrulation is a vital development stage in which embryonic cells become primed to form different organs and tissues. The human cells took longer to reach this point than the monkey ones did. But they managed nevertheless, providing more evidence that the human cells were not merely passive passengers, but were "mucking in" to help with the process of embryonic development.
这些细胞是在实验室里生长的,这带来了局限性。到了第15天,存活的胚胎数量开始下降。到第20天已一无所剩。但这段时间已经足以发生一个名为“原肠胚形成”的过程。原肠胚形成是一个至关重要的发育阶段,胚胎细胞在此期间准备好形成不同的器官和组织。人类细胞达到这个节点所花的时间比猴子细胞更久,但它们还是做到了。这就提供了更多证据,证明人类细胞不仅仅是被动的搭乘者,而是在“一同出力”帮助了胚胎的发育过程。
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