DNA recorders reconstruct cellular family trees in developing mice

Howard Hughes Medical Institute reported on October 8 that teams at the Whitehead Institute and the University of Washington had reconstructed cellular family trees spanning millions of cells in developing mice. The experiments use DNA recordings to trace how cells acquire different identities, offering a way to study development hidden inside the mother.

In its announcement reproduced by Phys.org, HHMI describes the results from teams led separately by Jonathan Weissman and Jay Shendure as the most complete mammalian lineage maps yet made. It says the work is published in Science. That assessment comes from the institutional account; an earlier, independently authored Nature study provides context for the recording approach.

How DNA records a cell’s ancestry

A transparent roundworm embryo allows researchers to watch cells divide under a microscope. A mouse embryo develops inside its mother, making continuous observation of its development much harder. The recording systems address that visibility problem by leaving biological records that scientists can examine later.

Both approaches engineer cells to accumulate inheritable DNA marks. Descendants carry marks from their ancestors alongside subsequent changes. Reading those combinations lets researchers infer which cells share a developmental history and assemble a family tree. The result is a retrospective reconstruction, rather than a continuous visual record of an embryo growing.

PEtracer and DNA Typewriter take different starting routes

Weissman’s team introduced PEtracer in 2025. According to HHMI, it uses prime editing to install marks at more than 100 sites in the genome. The newly reported milestone is its application to mouse development, extending a tool the researchers had already developed.

For that experiment, the Whitehead Institute team engineered stem cells with the recording system and injected them into an embryo. HHMI says the developing embryo incorporated the marks into nearly every cell it produced. That description concerns the spread of the marks; it does not establish that researchers sequenced every cell.

Single-cell sequencing reads the inherited records together with information about cell identity and gene expression. This connects what sampled cells have become with their inferred ancestry, helping researchers examine how different types of cells emerge and commit to particular developmental fates.

Shendure’s University of Washington team developed DNA Typewriter in 2022. It also uses prime editing, recording successive information on a DNA sequence that HHMI likens to ticker tape. In the new experiment, researchers injected its components directly into a fertilized mouse egg, allowing marks to accumulate as development proceeded.

The scope is embryonic development. The Science paper identified in the announcement is titled “A DNA Typewriter records the cell lineage history of a mouse, from zygote to late organogenesis.” An accompanying image caption identifies an embryo at embryonic day 13.5. Neither establishes a complete map of every cell in an adult mouse.

Earlier research recorded development and precancer

Recording mammalian cellular histories has experimental precedent. Mirazul Islam, Ken S. Lau and colleagues published “Temporal recording of mammalian development and precancer” in Nature on October 30, 2024. Their independently authored study combined genetic histories with single-cell measurements to investigate when cellular events occurred.

That study used self-mutating CRISPR barcodes, gene-expression measurements and mitochondrial variants to examine mouse embryos at days 7.75, 8.5 and 9.5. It reported tissue-specific differences in cell expansion and developmental relationships between cell types, demonstrating that genetic records could reveal aspects of mammalian development before the latest announcement.

The Nature researchers also identified obstacles in earlier barcoding strategies, including restricted barcode diversity and loss of recorded information through large deletions. Those limitations help explain why recording design matters. The new HHMI account does not establish that PEtracer or DNA Typewriter eliminates every recording error.

Disease research and virtual embryos remain proposed uses

HHMI identifies possible applications in studying tissue differentiation, embryos’ vulnerability to genetic or environmental stress, and how tumors begin, spread or become resistant to therapies. These are research directions described in the announcement, rather than demonstrated clinical benefits from the new mouse experiments.

The institute also says the data will be used to train AI models of embryogenesis, with a predictive “virtual embryo” as an ultimate goal. Its report supplies neither demonstrated prediction accuracy nor a completed virtual-embryo result.