The woolly mammoth is on the verge of de-extinction
Scientists have made a stem cell breakthrough in elephants that could mean researchers are one step closer to bringing back long-extinct woolly mammoths. Colossal Biosciences’ woolly mammoth team says it has successfully derived induced pluripotent stem cells (IPSCS) from Asian elephants. IPSCS are cells that have been reprogrammed so they can give rise to any cell type in the body, meaning researchers will now be able to investigate the adaptations that differentiate woolly mammoths from their closest living relatives and test gene edits without having to take tissue from living animals.
“These cells are a great benefit to our de-extinction work,” said Eriona Hysolli, head of biological sciences and mammoth lead at Colossal Biosciences. What’s crucial about them is that they can reveal the cellular and genetic processes behind features that helped woolly mammoths thrive in the Arctic. These features include shaggy hair, curved tusks, fat deposits and a dome-shaped cranium. IPSCS also open a path to creating elephant sperm and egg cells, which are essential for mammoth de-extinction, in the lab. With fewer than 52,000 Asian elephants left in the wild, harvesting cells from these animals would prove difficult and undesirable.
Previously, deriving elephant IPSCS proved challenging because these animals have a complex gene pathway not found in other species. The researchers overcame this by suppressing core genes called TP53 that regulate cell growth and prevent cells from duplicating indefinitely. “One of the things that we had to overcome for elephant cells is that they do have this expansive TP53 pathway,” Hysolli said. “We had to suppress this pathway via two means in order to get these IPSCS, so we had to go through a multi-step process in order to achieve them.”
The breakthrough may also shed light on early development in elephants, which is currently considered the biggest hurdle to woolly mammoth de-extinction. If researchers succeed in creating a woolly mammoth embryo by fusing ancient mammoth DNA with elephant cells, they will need to implant this embryo into an elephant surrogate to complete a 22-month gestation period. Engineering a woolly mammoth embryo no longer poses a huge challenge, but birthing a healthy calf will take time and work. The team is still researching alternative methods to generate elephant IPSCS and maturing the ones they have newly developed. The IPSCS breakthrough, which will be published on the preprint database biorxiv, has yet to be peer-reviewed.
“There is more validation to be done, so until you do the experiment you can never be sure, but we think that the pluripotency potential [to differentiate into any cell type] is fully there,” Hysolli said. This is an important breakthrough and an essential step to create a woolly mammoth-like elephant. “The goal is to turn these IPSCS into sperm and eggs, which would allow for in-vitro fertilisation and eventually surrogacy,” said Vincent Lynch, a developmental biologist and associate professor at the University at Buffalo in
New York. “Those methods are pretty challenging and haven’t been developed yet, but it is only a matter of time.”