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Scientists have traced the development of budding zebrafish and frog embryos over the first 24 hours of life, down to the single cell.

Harvard Medical School researcher Allon Klein and his colleagues used a technique called single-cell sequencing to detail how an egg made of just one cell divides and forms a slew of different cell types. Their findings give researchers a guide to the very earliest stages of cellular-decision making.

“In one snapshot, we can see the entire story of development unfolding,” said Klein.


STAT chatted with Klein about the work, published Thursday in Science.

How did you capture the development of embryos?

We can take the developing embryo, gently dissociate it into single cells, study each individually. And then very rapidly, before the cells realize they’re in a different environment, we capture the cells in nanoliter-scale droplets. Each one of these droplets acts as a reaction chamber in which we can individually process information from each cell. We add a little DNA barcode to each cell, then break the droplets and pool the materials back together. Then we can use the DNA barcodes to figure out which material came from which cell.


What does that tell you about how a single cell becomes a complex organism?

We wanted to study decision-making of cells as a dynamic process over time. Embryos are really fascinating because they start off as a single cell. And then at some point, the embryo starts to generate organs, tissue, skin, the brain, and muscle. By capturing cells over the first 24 hours of life, we could look at the entire process by which cells were making decisions about the cell types they were going to become. In that amount of time, a zebrafish embryo has developed 70 different cell types and the heart has started beating.

How can other scientists use that information?

This is going to be an incredible resource for people trying to understand cell decision-making. And many researchers now are trying to create cell types for therapeutic purposes, like creating blood cells in a dish to be used in transfusions. We now have a very accurate description of how cells go from an undifferentiated state to having an identity. This would be useful if you’re trying to figure out which signaling pathways are needed or which transitional states a cell has to go through before it gets to the right endpoint. We could also use it to look at the dynamic of diseases such as developmental disorders or tumor development.