Researchers in China have achieved the first live birth of a chimeric primate – a monkey with cells from two genetically distinct embryos from the same species.
The study, published in the journal Cell, could have implications for genetic engineering, conservation and other biomedical research.
Chimeras are single organisms composed of the cells of more than one genetically distinct individual. They are associated with Greek mythology. Among the best-known examples in mythology are griffins (half lion, half eagle) and the three-headed monster Chimera itself (part lion, part snake, part goat).
But chimerism is not just myth. It exists in nature and through human intervention.
Sponges and ants are examples of organisms that exhibit chimerism in nature. Plant grafting is an example of human-induced chimerism. Marmosets (small monkeys found in South America) display germline chimerism where an individual can carry the reproductive cells (egg or sperm cells) of their fraternal twin siblings due to fusion of the embryos during development.
Chimerism has even been found in humans.
Previously, chimerism has been induced in rat and mouse embryos who were born with a high proportion of cells derived from genetically distinct individuals through the genetic manipulation of stem cells. The new study is the first time it has been demonstrated in primates.
“This is a long-sought goal in the field,” says senior author Zhen Liu of the Chinese Academy of Sciences (CAS). “This research not only has implications for understanding naive pluripotency [the ability of particular cell types to differentiate into other types of cell] in other primates, including humans, but it also has relevant practical implications for genetic engineering and species’ conservation. Specifically, this work could help us to generate more precise monkey models for studying neurological diseases as well as for other biomedicine studies.”
Cynomolgus monkeys (also known as crab-eating or long-tailed macaques) were used in the study. These primates are native to Southeast Asia.
Nine stem cell lines using cells removed from 7-day-old embryos were labelled with a green fluorescent protein and injected into 4–5-day-old embryos. These embryos were then implanted into female macaques, resulting in 12 pregnancies and 6 live births.
The green protein glowed, proving chimerism, in one monkey which was born alive and another monkey which was miscarried.
Gene sequencing showed that the stem cell-derived cells were present in the brain, heart, kidney, liver and digestive system of the monkeys. In the live monkey, stem cell-derived cells ranged from 21% to 92%, with an average of 67% across the 26 different types of tissue tested. The numbers were lower in the still-born monkey foetus.
“In this study, we have provided strong evidence that naive monkey pluripotent stem cells possess the capability of differentiating in vivo into all the various tissues composing a monkey body,” says co-corresponding author Miguel Esteban of CAS. “This study deepens our understanding of the developmental potential of pluripotent stem cells in primate species.”
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