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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.”

 ?? ?? Woolly mammoths were well equipped for snow-covered landscapes
Woolly mammoths were well equipped for snow-covered landscapes

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