It takes three weeks for a mouse to develop from a fertilized egg into a newborn. In that time, there are four days that arguably matter more than all the rest.
Right around day number nine, the embryo undergoes rapid changes that form the mouse’s major organs from germ layer cells.
Researchers at the University of Washington mapped this period of organ development in mice using RNA sequencing tools and published the results today in the journal Nature. The resulting dataset will serve as a reference point for how developmental diseases work on a genetic level.
“The goal of this study was to build a map of how organ development normally occurs,” said Jay Shendure, an author on the paper and a professor of genome sciences at the University of Washington.
The next step will be to look at abnormal development in embryos that have been genetically modified to contain known developmental diseases. The gene expressions of the two groups can then be compared to give researchers an idea of what goes wrong genetically.
“To the best of my knowledge, this will be the largest single cell dataset that’s been published,” Shendure said.
Single cell measurements look at which genes are being expressed, or “turned on,” in cells. Shendure and his team used a technique called single-cell combinatorial indexing to do this on a large scale. Their work analyzed approximately 2 million cells from 61 embryos between 9 and 14 days old.
Shendure co-authored the paper with fellow UW professor Cole Trapnell, graduate student Junyue Cao and postdoc Malte Spielmann. Shendure won the 2019 Richard Lounsbery Award from the National Academy of Sciences for developing technologies that make DNA sequencing faster, cheaper and more useful.
The mouse study will help scientists understand how developmental diseases work in humans, Shendure said.
“We’re a thousand times bigger, but we’re not a thousand times more complex.”