How do cells write their own history?

Instead of watching development happen, the researchers made cells record it in their own DNA. The trick works like this:

• Each time a cell divides, it adds a small, permanent mark to its genome.
• Both daughter cells inherit that mark.
• The daughters add new marks when they divide in turn.
• Sequencing each cell at the end reveals the full chain of marks — and with it, the cell's complete ancestry.

Because researchers read the marks by sequencing individual cells, the same experiment shows both what a cell became — its type and the genes it is expressing — and where it came from.

"The cell divides and each of the sisters gets a mark, and those are inherited by their daughters, and they get additional marks, and so on and so forth," Weissman said. "And so, by looking at the end at the marks in this DNA, we're able to reconstruct what this relationship is."

What tools did each team use?

Weissman's team unveiled a technique called PEtracer in 2025. It uses prime editing — a precise genome-editing method — to install heritable marks at more than 100 sites in the genome. The researchers engineered mouse stem cells carrying these marks and injected them into an embryo. As the embryo developed in utero, the marks spread into nearly every cell it produced.

Shendure's team developed a related technology in 2022 called DNA Typewriter, which also uses prime editing to log each cell division onto a string of DNA, like entries on a ticker tape. In the new work, his team injected the DNA Typewriter components directly into a fertilized mouse egg, and the marks accumulated as the embryo's cells divided.

By analyzing the resulting records, both teams traced how cells commit to their fates as the animal develops — the moment, for example, when a cell's descendants are locked into becoming muscle, nerve, or blood.

What could the maps be used for?

The new lineage maps open several research directions:

• Understanding normal development, including how cells differentiate to build tissues.
• Identifying where and when a developing embryo is most vulnerable to environmental or genetic stressors.
• Studying how tumors initiate, grow, spread, and become resistant to therapies.
• Training AI models of embryogenesis, with the long-term goal of building a "virtual embryo" that can predict developmental outcomes.

"There are so many key things that happen during development or during the evolution of a tumor that are happening at a time when we can't observe them directly, so if we can record that information in the DNA, then we can infer and reconstruct exactly how it's happening," Weissman said.

He added that the tools could yield "unknown unknowns" — discoveries nobody can anticipate, much as the roundworm cell map of the 1980s led to unexpected biological insights. "That was just by understanding the process and getting at the underlying molecular mechanisms that led to those discoveries," he said.