2023-11-10 12:11:58
Photographs taken three days after the birth of the chimeric macaque “number 10”, presenting fluorescent tissues (arrows), obtained by Chinese teams. CELL/CAO ET AL.
In recent years, China, a hub for studies on non-human primates, has accustomed us to scientific firsts featuring adorable little monkeys. At the beginning of 2014, the magazine Cell revealed the birth of Lingling and Mingming, the first two primates whose genome was modified using Cripsr-Cas9, then a completely new DNA editing technique. In 2018, there was Zhong Zhong and Hua Hua, the first successful cloning of two primates, twenty-two years after the Dolly sheep in Edinburgh (United Kingdom). At the beginning of 2019, five other cloned Chinese macaques, copies of a specimen genetically modified to present circadian rhythm disorders, experienced some resonance, followed by other anonymous monkeys with partially humanized brains.
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No little name either for the crab-eating macaque “number 10”, born two and a half years ago in Shanghai and presented on November 9 in the magazine Cell by a team led by Zhen Liu (Institute of Neuroscience of the Chinese Academy of Sciences, Shanghai). With its eyes and nails taking on a greenish glow under fluorescent light, the little animal only survived ten days before its health deteriorated to the point of having to undergo euthanasia. It is the first example of the birth of a chimeric monkey presenting a high concentration of cells coming from an individual other than the embryo from which it came.
Scientists have known how to make such chimeras in mice for more than thirty years. This technique makes it possible to obtain genetically modified lines which can notably serve as models for studying human diseases. But in non-human primates, it remains ineffective and very expensive.
The birth of “number 10” could pave the way for such models in primates. The recipe remains complex and imperfect. It first consists of extracting stem cells from a first macaque embryo and modifying them genetically – in this case to make them express a green fluorescent protein (GFP) from a jellyfish. These embryonic stem cells are then introduced into another embryo cultured in vitro. The whole thing is then implanted into a surrogate mother.
Shifting to a form of interspecies chimerism
Chinese researchers had to test numerous combinations of culture media for this “chimeric graft” to take. And again, the 74 embryos showing clear signs of fluorescence transferred into forty surrogate mothers resulted in twelve reported pregnancies and only six full-term births. But, ultimately, chimerism was only maintained in an aborted male fetus and in “number 10” – a male who had received female cells! Everywhere else, the host embryo had eliminated the donor cells.
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