A Stanford-led study on the acorn worm Schizocardium californicum provides strong evidence that extensive cellular reprogramming occurs during normal metamorphosis, not just after injury or during regeneration.

The study tracked labeled larval cells through metamorphosis, confirming that cells persist into adulthood while changing their identities, rather than undergoing large-scale cell death and replacement.

Muscle and mesoderm cells largely retained their larval-to-juvenile functions, indicating that reprogramming is not uniform across all cell types.

The research was published in Nature Communications on September 8, 2026, with contributions from Stanford and collaborators at Baylor College of Medicine, Chan Zuckerberg Biohub, Johns Hopkins, Stowers Institute, UC Berkeley, and others, funded by Chan Zuckerberg Biohub Intercampus Research Award and the National Science Foundation.

Schizocardium californicum, an indirect developer within the hemichordata phylum, provides a crucial link to vertebrates and mammals, highlighting the relevance of non-model organisms for evolutionary developmental biology.

This work is significant because it demonstrates extensive cellular reprogramming in a bilateral-developing animal, a finding previously observed mainly in non-bilaterian organisms like sponges and jellyfish, and it broadens understanding of metamorphosis across evolution.

The findings constitute the strongest evidence to date for developmental reprogramming in a bilaterally symmetric animal, expanding understanding of metamorphosis beyond invertebrates like sponges and jellyfish to include a hemichordate with evolutionary links to vertebrates.

The investigation highlights the role of non-model marine organisms in revealing fundamental developmental processes and challenges the traditional view that metamorphosis primarily involves cell death and replacement or simple functional retention.

Researchers conducted the study at Stanford’s Hopkins Marine Station and related institutions, with Paul Bump as first author and Christopher Lowe as senior author, and published the results in Nature Communications.

Single-cell RNA sequencing of over 87,000 cells across five developmental stages revealed that larval cells are more similar to other larval cell types than to their corresponding adult cell types, indicating widespread reprogramming during metamorphosis.

Single-cell RNA sequencing identified 12 cell classes and showed that many larval cell types are more similar to each other than to their adult counterparts performing the same functions, indicating extensive cellular reprogramming rather than widespread cell death or simple fate retention.