In a Kenyan wildlife conservancy near the equator, armed guards protect two northern white rhinoceroses, Najin and Fatu. They are the last two northern white rhinos alive—both non-reproductive females—making the species functionally extinct.
For several years, Jeanne Loring, a stem cell biologist at Scripps Research Institute, along with other scientists, has explored ways to rescue these animals from eventual extinction. In 2011, Loring and her team created the first induced pluripotent stem cells (iPSCs) from the skin cells of northern white rhinos.1 They eventually expanded the collection to include cells from nine rhinos. “The ultimate goal is to make eggs out of these iPSCs and to fertilize them, either with sperm made from iPSCs or sperm that have been stored from animals that are now dead,” explained Loring.
However, there was no way to assess the quality of the iPSCs to prevent transmitting genetic defects to the gametes or embryos. Now, Loring and her team mapped the complete genome of a northern white rhino, providing a reference to analyze the integrity of iPSCs, as per a study published in the Proceedings of the National Academy of Sciences.2 “With this tool in hand, we can actually identify those cell lines which are fit for [the] purpose [of generating] germ cells,” said study coauthor Franz-Josef Müller, whose work focuses on stem cells and genomics at the Max Planck Institute for Molecular Genetics.
Loring, Müller, and their team assembled the reference genome from fibroblasts that were originally collected and frozen in 1997 from Angalifu, a male northern white rhino who died in 2014. This was no small feat. “Getting DNA from a northern white [rhino] across borders is almost impossible,” said Müller. So, one of their team members flew from Germany to California with a palm-size nanopore sequencer to carry out sequencing there, he recalled. Their efforts eventually paid off: They built a good-quality genome with very few gaps.
Müller and his team visited a southern white rhinoceros, Dino, at Schwerin Zoo.
University Hospital Schleswig-Holstein
Equipped with a reference genome, the researchers set out to assess the integrity of one of the iPSC lines that they had created from Angalifu’s fibroblasts, which were preserved in San Diego Zoo Wildlife Alliance’s Frozen Zoo®, a large animal-cell biobank, in 2021.3 Comparing the iPSC genome with the reference revealed that the iPSC genome was missing a large chunk of DNA. This deletion of 30 million base pairs affected more than 200 genes, including those associated with cell cycle function and tumor suppression. Neither Loring nor Müller were surprised by these deletions as iPSCs, which divide indefinitely, are known to rapidly acquire mutations in culture.4 The reference genome can help researchers identify iPSC lines with the least harmful mutations for developing gametes.
Mutations in iPSCs are not surprising, agreed Desire Lee Dalton, a wildlife conservation geneticist at Teesside University, who was not associated with the study. “And that kind of shows that you do have to have this rigorous quality control of these stem cell lines before you implant [embryos made from] them,” she said.
Researchers found that the genomes of northern and southern white rhinoceroses (top) are similar.
University Hospital Schleswig-Holstein
Loring, Müller, and their team also used the newly assembled reference genome to understand the differences between northern and southern white rhinoceroses. Conservation efforts helped bring southern white rhinos back from the brink of extinction in the 2000s and scientists proposed using them as surrogates for northern white rhino embryos.5 Comparing the northern white rhino genome with a previously-established southern white rhino genome revealed a high degree of similarity between the two, suggesting that the latter can serve as surrogates without major complications.
“This [research] has a very, very good study design,” said Dalton. Although she said that this study represents an important step in the efforts to save the northern white rhino, she explained that researchers in the field are divided on whether to bring back extinct species or focus on saving others on the brink of extinction. “If they do bring [northern white rhinos] back, what are we going to change now that we didn't change back then that caused them to be extinct?”
But Loring is hopeful. She believes that their study puts in motion the steps required to save endangered species. “But we are not going to try to de-extinct anything,” she added. “This is not the way that we would bring back a T. rex or a woolly mammoth or a dire wolf.” Müller agreed, adding that he hopes that their study can create a positive example that inspires people to find solutions and work collaboratively.
- Ben-Nun IF, et al. Induced pluripotent stem cells from highly endangered species. Nat Methods. 2011;8(10):829-831.
- Wang G, et al. Genomic map of the functionally extinct northern white rhinoceros (Ceratotherium simum cottoni). Proc Natl Acad Sci USA. 2025;122(20):e2401207122.
- Korody ML, et al. Rewinding extinction in the northern white rhinoceros: Genetically diverse induced pluripotent stem cell bank for genetic rescue. Stem Cells Dev. 2021;30(4):177-189.
- Laurent LC, et al. Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture. Cell Stem Cell. 2011;8(1):106-118.
- Saragusty J, et al. Rewinding the process of mammalian extinction. Zoo Biol. 2016;35(4):280-292.
