The recordings covered the first 13.5 days of embryonic development, offering an unusually detailed view of how a complex mammalian body takes shape. A mouse’s complete gestation lasts approximately 19 to 21 days.

The findings were published in Science on Oct. 8, 2026. The research could help scientists better understand normal development—and what happens when that process goes wrong.

“We are interested in tracing how a cell’s early ancestry in the embryo influences its subsequent fate. Exploring cell lineages can help decipher normal development. Such research could ultimately advance our knowledge about congenital malformations, neurodevelopmental conditions, genetic diseases, or cancer,” said Jay Shendure, Ph.D., professor of genomic sciences at the University of Washington School of Medicine in Seattle and a Howard Hughes Medical Institute research fellow.

Shendure led the study with Chenxian Qiu, Ph.D., a molecular and systems biologist at Dartmouth College in New Hampshire. Both researchers served as senior authors.

How a DNA typewriter records the history of living cells

The achievement was made possible by a technology called the DNA typewriter, developed by Shendure and Junhong Choi, who now works at Memorial Sloan Kettering Cancer Center.

The system stores a record of a cell’s history directly within its DNA instead of simply observing cells as they divide.

To create the system, researchers inserted a redesigned recording sequence, known as a tape, into the genome of a fertilized mouse egg. The updated design makes it easier to recover the information stored in individual cells.

As the embryo developed, the DNA typewriter remained embedded in the cells’ genetic material. It recorded cell divisions in a format that could later be used to reconstruct each cell’s ancestry. The result functions like a biological diary documenting the sequence of events that produced different cell populations.

“Think of it like a real typewriter, except instead of paper, you type the cell’s own DNA,” explained study co-lead author Haedong Kim, a genome science postdoctoral fellow at UW Medicine, the Seattle Synthetic Biology Hub, and the Howard Hughes Medical Institute. “Each time a cell divides, a new letter is added to the next blank line, always in sequence and never overwriting an existing letter. Because the letters are always filled in in sequence, the order itself represents the cell’s division history.”

These markings are passed to daughter cells. By comparing the recorded sequences, researchers can identify cells descended from a common ancestor. Cells with matching portions of the record can then be connected, allowing scientists to reconstruct branches of an embryo’s cellular family tree.

“Writing the records is only half the problem; we also have to read the records from each cell, so we redesigned the tape to make that easier,” Kim said.

A new way to overcome challenges in developmental biology

Reconstructing the complete developmental history of a mammal has long been difficult. As an embryo grows, its cells divide repeatedly and begin taking on specialized functions. As the number and variety of cells increase, their relationships become increasingly difficult to follow.

Scientists achieved a similar feat decades ago with tiny roundworms, which have relatively simple bodies and far fewer cells. Their transparency also makes it easier to study development.

Mammals are considerably more complex. Earlier techniques provided important insights into mouse embryonic development but generally captured only part of the larger cellular family tree.

Some traditional lineage-recording methods work by cutting DNA to create identifying marks. This can damage cells and erase information from earlier divisions. Because recording capacity is limited and the marks are not always created in a fixed order, scientists must later try to reconstruct the sequence of events.

“The DNA typewriter avoids all of this,” Kim said. “Because it writes the DNA without cutting it completely, records relatively stably, and writes everything in a strict order, it allows us to record cell lineages at higher resolution and over longer periods of time.”

Tracing the embryo back to its first two cells

The researchers began by recording the development of 100 fertilized mouse eggs. Ultimately, 10 embryos were available for analysis.

One specimen, identified as Embryo No. 3, stood out because its DNA recording system performed particularly well and preserved the most extensive developmental history. Researchers therefore focused their detailed analysis on that embryo.

One of the most important findings came from recordings made shortly after the fertilized egg divided for the first time.

“Our recordings captured clear and persistent marks that differentiated the first two cells, and we were able to trace nearly every cell we profiled back to either side of the embryo,” Kim said. “One of these two founder cells continued to produce more progeny than the other, but they produced diverse cell types in roughly equal proportions.”

In other words, both founder cells produced a surprisingly similar mix of specialized cell types, even though one original cell generated more descendants overall.

The result demonstrates how the DNA typewriter can reveal early developmental events at a level of detail that has previously been difficult to achieve.

When do embryonic cells choose their roles?

The DNA record also revealed when cells began committing to their eventual roles in the body.

Early embryonic cells can develop into several tissue types. As development continues, their descendants gradually specialize, eventually contributing to structures such as the nervous system, skin, blood, and eyes.

By reconstructing the branches of the embryo’s cell family tree, researchers determined when different groups of cells began following distinct developmental paths.

The observations were consistent with conclusions from decades of previous research, but the new approach allowed scientists to examine these patterns within a single developing mouse.

“While blood cells and the retina committed relatively early, the outer layer of the skin did not commit until much later,” the researchers explained. “Cell fate was not determined all at once; different cell types settled on their identities on separate schedules, some early and some late.”

The findings indicate that the transition from flexible, unspecialized cells to cells with specific biological functions does not happen simultaneously throughout the embryo.

Instead, different cell populations follow their own developmental timelines. Some begin narrowing their future potential early, while others remain flexible for longer periods before committing to a specific role.

Implications for birth defects, cancer, and stem cell therapy

Understanding exactly how cells acquire their identities could eventually have important implications for medicine.

Many developmental disorders occur when cell specialization or tissue formation is disrupted. Cancer also involves abnormal cell behavior, including failures in the mechanisms that regulate growth and division.

By tracing cell ancestry and identifying when developmental pathways emerge, scientists may gain a better understanding of how these problems begin.

“These kinds of large-scale developmental records give scientists a map of how one cell becomes a whole body. This can help explain how organs form correctly, how the process goes wrong in birth defects, and how abnormal cell growth causes cancer. As stem cell engineering advances, these kinds of records can also help guide how to manipulate cells for therapeutics.”

The research was conducted in mouse embryos and does not yet result in direct treatments. However, it provides a powerful method for studying the biological decisions that shape developing organisms.

The approach could also support future stem cell research, particularly efforts to direct cells toward specific identities for regenerative medicine and other therapeutic applications.

Research team and funding

Other co-lead authors include Qi Yu and Sophie Seidel of the University of Washington School of Medicine’s Department of Genomic Sciences and the Seattle Synthetic Biology Hub.

Shendure is chief scientific director of the Seattle Synthetic Biology Hub. He is also scientific director of the UW Medicine Brotman Baty Institute for Precision Medicine and the Allen Institute for Cell Lineage Tracing.

The research received support from the Seattle Synthetic Biology Hub, a collaboration involving the Allen Institute, Biohub, and the University of Washington School of Medicine (CZIF2023-008738); the Paul G. Allen Frontiers Group’s Allen Discovery Center for Cell Lineage Tracing; the UW Medicine Brotman Baty Institute for Precision Medicine; the Washington Research Foundation; the National Institutes of Health (R00HG012973 and P30CA008748); the Damon Runyon Cancer Research Foundation (DFS-64-24); the Searle Scholar Award (SSP-2025-101); the Center for Quantitative Biology at Dartmouth, supported by the National Institute of General Medical Sciences (P20GM130454); and the Swiss National Science Foundation (239394).