This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Growing inside each of us is a cellular family tree. Every one of the 37 trillion cells in our body is generated from another cell, going all the way back to a single fertilized egg.
Much like we can draw a family tree tracking generations of our ancestors, scientists can also create family trees of cells, showing how they're related to each other. While researchers have created these family trees for simple, transparent animals like roundworms, generating a comprehensive cell fate map for a mammal, which develops in utero from a single fertilized egg to hundreds of millions of cells in just a few weeks, has remained out of reach. Now, HHMI investigators Jonathan Weissman and Jay Shendure and their teams have separately figured out how to do it.
Using new tools they created, the researchers have reconstructed cellular family trees spanning millions of cells in developing mice—the most complete lineage maps yet made for a mammal—and traced how those cells commit to their fates as the animal develops. The work is published in the journal Science. "It's really proof of principle that we can do what was done with the roundworm in 1983, but for mammals like you and me," Weissman says.
A roundworm embryo is transparent, allowing researchers to watch every cell divide under a microscope. In contrast, a mouse embryo develops inside the mother, hidden from view, so scientists cannot watch development in real time over long periods. Instead of observing this development, researchers have learned to make cells that can record it.
The idea is to engineer cells to write their own history into their DNA: Each time a cell divides, it adds a small, permanent mark to its genome. Those marks are inherited, so every cell carries a record of its ancestry that can be read out long after the divisions occurred. In 2025, Weissman and his team unveiled a new version of this technique they call PEtracer, which uses prime editing to install these marks at more than 100 sites in the genome.
"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 says. "And so, by looking at the end at the marks in this DNA, we're able to reconstruct what this relationship is." Because the marks are read out by sequencing individual cells, the same experiment reveals both what a cell has become—its type and the genes it is expressing—and where it came from. In new research, Weissman and his team at the Whitehead Institute applied PEtracer to study mouse development.
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