Bringing Back the Mammoth: The Advancements in Using Induced Pluripotent Stem Cells to Resurrect Extinct Species

Tuesday - March 12 2024, 21:14 UTC - 10 months ago

Despite the challenges of obtaining cells from endangered Asian elephants, biotechnology company Colossal has made a major breakthrough by successfully transforming elephant skin cells into stem cells. These induced pluripotent stem cells (iPSCs) will be crucial in the project to bring back the woolly mammoth through gene editing and embryo implantation. The technology was first developed nearly two decades ago and has revolutionized biology, but has been especially difficult to apply to elephants.

The last woolly mammoth roamed the vast arctic tundra 4,000 years ago. Their genes still live on in a majestic animal today—the Asian elephant. With 99.6 percent similarity in their genetic makeup, Asian elephants are the perfect starting point for a bold plan to bring the mammoth—or something close to it—back from extinction. The project, launched by biotechnology company Colossal in 2021, raised eyebrows for its moonshot goal.

The overall playbook sounds straightforward. The first step is to sequence and compare the genomes of mammoth and elephant. Next, scientists will identify the genes behind the physical traits—long hair, fatty deposits—that allowed mammoths to thrive in freezing temperatures and then insert them into elephant cells using gene editing. Finally, the team will transfer the nucleus—which houses DNA—from the edited cells into an elephant egg and implant the embryo into a surrogate. The problem? Asian elephants are endangered, and their cells—especially eggs—are hard to come by. Last week, the company reported a major workaround. For the first time, they transformed elephant skin cells into stem cells, each with the potential to become any cell or tissue in the body.

The advance makes it easier to validate gene editing results in the lab before committing to a potential pregnancy—which lasts up to 22 months for elephants. Scientists could, for example, coax the engineered elephant stem cells to become hair cells and test for gene edits that give the mammoth its iconic thick, warm coat. These induced pluripotent stem cells, or iPSCs, have been especially hard to make from elephant cells. The animals 'are a very special species and we have only just begun to scratch the surface of their fundamental biology,' said Dr. Eriona Hysolli, who heads up biosciences at Colossal, in a press release. Because the approach only needs a skin sample from an Asian elephant, it goes a long way to protecting the endangered species. The technology could also support conservation for living elephants by providing breeding programs with artificial eggs made from skin cells. 'Elephants might get the 'hardest to reprogram' prize,' said Dr. George Church, a Harvard geneticist and Colossal cofounder, 'but learning how to do it anyway will help many other studies, especially on endangered species.' .

Turn Back the Clock .

Nearly two decades ago, Japanese biologist Dr. Shinya Yamanaka revolutionized biology by restoring mature cells to a stem cell-like state. First demonstrated in mice, the Nobel Prize-winning technique requires only four proteins, together called the Yamanaka factors. The reprogrammed cells, often derived from skin cells, can develop into a range of tissues with further chemical guidance. Induced pluripotent stem cells (iPSCs), as they're called, have transformed biology. They're critical to the process of building brain organoids—miniature balls of neurons that spark with activity—and can be coaxed into egg cells or models of early human embryos. The technology is well-established for mice and humans. Not so for elephants. 'In the past, a multitude of attempts to generate elephant iPSCs have not been successful, despite being so critical for most applications of iPSCs,' said Dr. Jeanne Loring, a stem cell biologist at the Scripps Research Institute, in an email to Singularity Hub. The roadblock isn't for lack of trying.