Images showing green fluorescence signals in different parts of the body of a 3-day-old chimera monkey. Credit: Cell/Cao et al.
A breakthrough in primate research: The birth of the chimeric ape
Chinese researchers have announced the first live birth of a chimera monkey, a major breakthrough in primate research. This achievement opens new horizons for understanding stem cell pluripotency, and has important implications for genetic engineering and biomedical studies.
A team of researchers in China has reported for the first time the live birth of a monkey containing a high percentage of cells derived from a monkey stem cell line. This “chimeric” monkey consists of cells that originate from two genetically different identical embryos Classify From the monkey. This has been previously demonstrated in rats and mice, but until now has not been possible in other species, including non-human primates. Details of the research were published November 9 in the journal cell.
Implications for multipotency and biomedical research
“This is a long-sought goal in the field,” says senior author Chen Liu of the Chinese Academy of Sciences (CAS). “This research not only has implications for understanding naïve pluripotency in other primates, including humans, but also has practical implications relevant to genetic engineering and species conservation. Specifically, this work can help us create more accurate monkey models to study Neurological diseases as well as other biomedical studies.
Study methodology
The monkeys used in the study were cynomolgus monkeys, also known as crab-eating macaques or long-tailed macaques, which are common primates in biomedical research. The researchers first created nine stem cell lines using cells taken from 7-day-old blastocyst embryos. They then placed the cell lines in culture to give them an enhanced ability to differentiate into different cell types.
They performed a number of different tests on the cells to ensure that they were multipotent, meaning that they had the ability to differentiate into all the cell types needed to form a living animal. The stem cells were also labeled with green fluorescent protein so that researchers could identify which tissues grew from which stem cells in which animals developed and survived.
Successful generation of chimeric monkeys
Ultimately, the scientists selected a specific subset of stem cells to inject into early monkey morula embryos (embryos that are 4 to 5 days old). The embryos were implanted in female macaques, resulting in 12 pregnancies and six live births.
One analysis confirmed that one monkey born alive and another aborted fetus were largely biochemical, containing cells grown from stem cells throughout their bodies. They were both male. The researchers used the green fluorescent protein marker to identify tissues containing cells derived from the injected stem cells.
They also used genetic sequencing and other tests to confirm the presence of stem cell-derived tissues across different organs. The types of tissue they tested containing stem cell-derived cells included the brain, heart, kidney, liver and gastrointestinal tract. In the living monkey, the contribution of stem cells to different tissue types ranged from 21% to 92%, averaging 67% across the 26 different tissue types tested. The numbers were lower in the monkey fetus.
In both animals, they also confirmed the presence of stem cell-derived cells in the testes and in the cells that eventually develop into sperm cells.
Future trends and improvements
“In this study, we provide strong evidence that naïve monkey pluripotent stem cells possess the ability to differentiate In vivo “In all the different tissues that make up the monkey’s body,” says co-author Miguel Esteban of BGI Research and CAS. “This study deepens our understanding of the developmental potential of pluripotent stem cells in primate species.”
“This work helps us better understand naïve pluripotency in primate cells,” adds co-author Qiang Sun from CAS. “In the future, we will try to increase the efficiency of this method of producing chimeric monkeys by improving the conditions for stem cell culture, blastocyst culture where stem cells are introduced, or both.”
The researchers also plan to further explore the mechanisms behind embryo survival in animal hosts, which they say will help improve the efficiency of chimera generation.
Reference: “Live Birth of a Chimeric Monkey with High Embryonic Stem Cell Contribution” by Jing Cao, Wenjuan Li, Jie Li, Md. Abdul-Mazid, Chunyang Li, Yu Jiang, Wenqi Jia, Liang Wu, Zhaodi Liao, Xu Sun, Weixiang Song, Jieqiang Fu, Yan Wang, Yong Lu, Yuting Xu, Yanhong Ni, Xinyan Bian, Changshan Gao, Xiaotong Zhang, Liansheng Zhang, Xinxin Zhang, Yunban Li, Lixin Fu, Hao Liu, Junjian Lai, Yang Wang, Yu Yuan, Shen Jin, Yan Li, Quanyu Liu, Yue Lai, Xueyang Shi, Patrick H. Maxwell, Xun Xu, Longqi Liu, Muming Bo, Xiaolong Wang, Qiang Sun, Miguel A. Esteban and Chen Liu, November 9, 2023, cell.
doi: 10.1016/j.cell.2023.10.005
This work was funded by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Key Project of Science and Technology of Shanghai Municipality, the Strategic Priority Research Program of the Chinese Academy of Sciences, and the Frontier Science Basic Research Program. From the Chinese Academy of Sciences, the National Key Program for Science and Technology Innovation 2030, and the Shenzhen Basic Research Project for Outstanding Young Researchers.
