Cellular reprogramming: A game-changer for endangered species

The process of cultivating iPSCs involves generating a starting cell type such as fibroblasts (a type of cell found in connective tissue), which are then reprogrammed into stem cells. Sylvester is optimizing and establishing a protocol to derive these starting cells from a simple blood sample, allowing researchers to capture and preserve existing biodiversity more effectively.

“The goal is that we go into the field and actually capture the existing biodiversity that allows species to survive today, and bank it so that we can access and learn from it,” Sylvester said.

The process uses a special protein called the SV40 large T antigen, which plays an important role in helping cells survive the extremely stressful reprogramming process. With this developed protocol, scientists can generate totipotent stem cells, capable of becoming any cell type, from almost any mammalian species. This breakthrough eliminates the often decades of research needed for species-specific iPSC generation.

“We can freeze samples as many times as we want and expand them as many times as we want,” explained Sylvester. “This allows us to directly study target species’ genetics, without the challenges of relying on model organisms, and improves the accessibility and longevity of genome resource banks.” 

Sylvester's path to conservation biology began in childhood, inspired by zookeeper and conservationist Steve Irwin. “I was always very interested in saving animals,” she said. “That passion was then coupled with a fascination of molecular science and how it could revolutionize the world of wildlife conservation.”

She pursued degrees in wildlife conservation and biological sciences from Virginia Tech, where she recognized the need for a molecular approach to preservation efforts. After graduation, she worked at the Smithsonian Institution as a research technician for the National Elephant Herpesvirus Laboratory and as an intern in the reproductive biology laboratory. Through a unique partnership, she continues her work with the Smithsonian while a graduate student at Cornell.

This research to safeguard species’ genetic diversity through this novel approach to the cultivation of iPSCs is urgent and fills a gap in existing conservation approaches. Today, the International Union for Conservation of Nature Red List identifies almost 7,000 threatened mammalian species. However, only 174 currently have breeding programs through zoos. Of these, only two are currently able to be managed by embryo-based technologies.

“We’re going to see animals going extinct before we have a chance to develop reproductive technologies,” Sylvester said. “Getting tissues or sperm samples is realistic in a zoological setting, but we’re missing all of the species that are actually existing right now in range countries.”

Importantly, the cultivation of iPSCs using the SV40 large T antigen has the potential to preserve entire ecosystems, rather than focusing solely on charismatic species—a common approach prevalent in current conservation efforts. “We have to not only preserve the ecosystem that the animal lives in for any conservation efforts to work, but also ameliorate the challenges that pushed that species towards extinction in the first place” said Sylvester. “For that, we need to buy time—which stem cells could provide.” 

Allowing for a more comprehensive approach to conservation is a key advantage of Sylvester's work. Traditional methods of creating iPSCs often require species-specific protocols, which can take decades to develop. Sylvester’s research has been successful for multiple species, including bison and mice. “We have evidence that our method works across species, which is huge because a lot of methods do not,” Sylvester said. 

Sylvester advocates for a more holistic ecosystem preservation strategy. This challenges traditional conservation paradigms and requires a more nuanced understanding of ecosystem dynamics, she explained. Preserving genetic raw materials will better allow nature to adapt to changing environments, ensuring a healthy, functioning biodiverse system. However, more funding and collaboration for this innovative approach is needed. 

Despite the challenges, Sylvester remains committed to her goal. "We don't know what the world's going to look like in 50 years," she said, "but we need to preserve as much genetic diversity as possible to give species the best chance to adapt and survive."

Caroline Stamm ’24 is a communications assistant for the Cornell CALS Department of Animal Science.