We’re a step closer to seeing a live woolly mammoth walking the Earth for the first time in 4,000 years. Colossal Biosciences, a company dedicated to the controversial-but-unquestionably-cool goal of resurrecting extinct species, has now announced a major breakthrough in creating elephant stem cells.
Apparently learning all the wrong lessons from Jurassic Park, Colossal Biosciences was formed in 2021 with the express goal of using genetic engineering to revive extinct animals. The woolly mammoth was the first target, but the company later expanded to bring back other iconic extinct species, the thylacine and the dodo.
But doing so is, well, a colossal undertaking. The scientists are comparing the genomes of mammoths and their closest living relatives, Asian elephants, which share 99.6% of their genes, and then tweaking the latter to be more like the former. That includes giving the offspring thicker hair, larger fat reserves, smaller ears and bigger tusks, all traits that help mammoths thrive in cold climates. This process means the resulting animal wouldn’t be a 'pure' mammoth but a hybrid.
The problem is, elephants are a difficult species to work with genetically. Now, Colossal has made a major breakthrough by coaxing adult elephant cells back to a state where they can differentiate into a range of other cell types. These so-called induced pluripotent stem cells (iPSCs) have been created for many other mammals, including humans.
“In the past, a multitude of attempts to generate elephant iPSCs have not been fruitful,” said Eriona Hysolli, Head of Biological Sciences at Colossal Biosciences. “Elephants are a very special species, and we have only just begun to scratch the surface of their fundamental biology. And now, using a multi-pronged approach to reprogramming we have the most successful efforts to date.”
Reprogramming any cell is difficult and inefficient, but in elephants it takes even longer. The hardest part is related to why elephants are resistant to cancer. Compared to other animals, they have a particularly complex TP53 pathway, which carefully regulates cell growth to prevent them becoming cancerous. The researchers found a way to suppress this pathway to finally allow them to reprogram the cells successfully.
In tests to validate them, the new elephant iPSCs have expressed several factors that show they’re viable, and were able to differentiate into the three germ layers that can go on to form every other cell type in the body. From this, the team should be able to start growing elephant cell lines in the lab, with the first goal to produce sperm and eggs in vitro.
While it’s a key step towards bringing the mammoth back from the dead, there’s obviously still a long way to go, and that lofty goal might never actually be reached. But the work along the way will still benefit elephants, the team says, including in assisted reproduction technologies that could help save them from following in their woolly ancestors’ footsteps.
The research is due to be published in a journal soon.
Source: Colossal Biosciences via Businesswire
