A study led by researchers from Stanford University has revealed that cells in acorn worms undergo significant reprogramming during their transformation from larvae to adults. This challenges earlier beliefs about how cells change during development. The study focused on Schizocardium californicum, a type of acorn worm that experiences a dramatic metamorphosis. Instead of the traditional view that larval cells die and are replaced by new adult cells, or that cells keep their original roles, the research found that many larval cells were reprogrammed to take on new functions in the adult, including becoming neurons. Published in Nature Communications, the study used a technique called single-cell RNA sequencing to analyze over 87,000 cells from Schizocardium californicum across five stages of development. The analysis grouped the cells into 12 categories, such as cartilage, immune, and skin cells. Researchers found that many larval cells were more similar to each other than to adult cells that performed the same roles. For example, larval neurons were more similar to larval gut cells than to adult neurons. This pattern was observed in more than half of the cells, suggesting widespread reprogramming. However, some cell types, like muscle and mesoderm cells, retained their functions from the larval to the juvenile stage. To confirm their findings, the researchers used a persistent dye to label some larval cells before metamorphosis. They observed that these cells remained in the adult organism, indicating that they were not dying in large numbers but instead changing into new cell types. This study is the first to show such extensive cellular reprogramming during normal development in an animal with a bilateral body plan, unlike previous research on sponges and jellyfish, which are not closely related to humans. Schizocardium californicum belongs to the phylum Hemichordata, which is thought to be an evolutionary link to vertebrates. The study emphasizes the value of studying "non-model" marine organisms, which may provide new insights into developmental biology and evolutionary history. Most commonly studied animals, such as mice and zebrafish, develop directly from an embryo into an adult, leaving a gap in understanding the development of animals that undergo metamorphosis. The study also compared Schizocardium californicum with its relative, Saccoglossus kowalevskii, a direct developer. While Saccoglossus kowalevskii has a worm-like shape from hatching, the larva of Schizocardium californicum looks very different from its adult form, indicating a dramatic transformation at both the physical and cellular levels.