•Scientists have reconstructed the cell lineage of an embryonic mouse. The 13.5-day process, from the moment of fertilization when the egg is divided in two, to the completion of the formation of the body and its organs, was recorded. (In mice, the full term of pregnancy is between 19 and 21 days.) The research results will be published in the journal Science on Thursday, October 8, 2026.
“We are interested in seeing how the early lineage of cells in the embryo influences what these cells will become in later stages. Studying cell lineages helps us to understand normal development. Such research could ultimately advance our knowledge of birth defects, neurodevelopmental conditions, genetics, genetic diseases, or cancer,” said Dr. Jay Shendure, professor of genomics at the University of Washington School of Medicine and a researcher at the Howard Hughes Medical Institute.
Together with Chengxiang Qiu, he is one of the co-authors of the Science paper. Qiu works as a molecular and systems biologist at Dartmouth College in New Hampshire.
Recording the cell history in DNA
The latest breakthrough was achieved using a tracking technology called the “DNA Typewriter,” invented by Shendure and Junhong Choi, who works at the Sloan Kettering Cancer Center.
The team inserted a redesigned tape into the genome of a fertilized mouse egg to use its DNA as a recording medium. The redesign makes it easier to read the tape back from the cells. As the cells acquire different characteristics to form the embryo, the DNA Typewriter remains within each cell’s own genetic material; it acts like the tail of a ship (the ship’s daily record). “Think of it like a real printer, but instead of paper, it writes on a cell’s own DNA,” said Haedong Kim, one of the study’s first authors, a postdoctoral scientist in genomics at UW Medicine and also a member of the Seattle Synthetic Biology Center and the Howard Hughes Medical Institute. “Each time a cell divides, it prints a single new character on the next blank line—always in sequence, without ever writing over what was previously written. Because the characters are always filled in sequentially, that line itself reveals the cell’s history of division.”
“DNA Typewriter avoids all of these,” said Kim. “It writes DNA without completely cutting it, maintaining a relatively stable record and writing everything in a precise sequence; so we can record cell lineages at much higher resolution and for much longer periods of time.” The researchers tested the recording system in 100 fertilized mouse eggs and obtained 10 embryos for analysis. The recording system clearly came into play in embryo No. 3, which had the richest history, and the scientists focused their analysis on it. Tracking the descendants of the first two cells The study yielded several new insights. One of them came from a fortunate event that was captured when the fertilized mouse egg was divided in two. “Our record captured a clear and permanent marker that distinguished the first two cells; so we were able to trace almost every cell we profiled from the embryo back to one of these two founding cells. One of these two cells produced more descendants, but both produced a nearly equal number of different cell types,” said Kim. Cell types follow different development schedules Another finding was that by analyzing the recordings, the scientists were able to determine when each cell type first branched off on its own developmental path. The results showed that the development tree of cell types, which helped scientists understand when cells choose their jobs. The findings were consistent with decades of accumulated research, but were measured here in a single mouse. “Blood cells and the outer layer of the skin committed relatively early, while the retina committed significantly later. The cell fate was not determined at the same time. Different cell types settled into their identities with their own separate schedules; some committed early, some committed later,” said Kim. Looking at the overall study, Kim said, “These large-scale developmental records provide scientists with a map of how a cell evolves into an entire body—how organs are formed correctly, how this process can go wrong with birth defects, and how abnormal cell growth leads to cancer. As stem cell engineering advances, this type of record can also help us engineer cells for therapeutic use.”
Other first authors of the study are Qi Yu and Sophie Seidel, both from the Department of Genomics at the UW School of Medicine and the Seattle Synthetic Biology Center, where Shendure is scientific director. Shendure is also scientific director of the UW Medicine Brotman Baty Institute for Precision Medicine and the Allen Cell Tracking Institute.
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