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Cell and Embryo Development Being Tracked in Unprecedented Detail

Accepted submission by takyon at 2018-12-25 06:46:32
Science

Development cell by cell [sciencemag.org]

From at least the time of Hippocrates, biologists have been transfixed by the mystery of how a single cell develops into an adult animal with multiple organs and billions of cells. The ancient Greek physician hypothesized that moisture from a mother's breath helps shape a growing infant, but now we know it is DNA that ultimately orchestrates the processes by which cells multiply and specialize. Now, just as a music score indicates when strings, brass, percussion, and woodwinds chime in to create a symphony, a combination of technologies is revealing when genes in individual cells switch on, cueing the cells to play their specialized parts. The result is the ability to track development of organisms and organs in stunning detail, cell by cell and through time. Science is recognizing that combination of technologies, and its potential for spurring advances in basic research and medicine, as the 2018 Breakthrough of the Year.

Driving those advances are techniques for isolating thousands of intact cells from living organisms, efficiently sequencing expressed genetic material in each cell, and using computers, or labeling the cells, to reconstruct their relationships in space and time. That technical trifecta "will transform the next decade of research," says Nikolaus Rajewsky, a systems biologist at the Max Delbrück Center for Molecular Medicine in Berlin. This year alone, papers detailed how a flatworm, a fish, a frog, and other organisms begin to make organs and appendages. And groups around the world are applying the techniques to study how human cells mature over a lifetime, how tissues regenerate, and how cells change in diseases.

The ability to isolate thousands of individual cells and sequence each one's genetic material gives researchers a snapshot of what RNA is being produced in each cell at that moment. And because RNA sequences are specific to the genes that produced them, researchers can see which genes are active. Those active genes define what a cell does.

That combination of techniques, known as single-cell RNA-seq, has evolved over the past few years. But a turning point came last year, when two groups showed it could be done on a scale large enough to track early development. One group used single-cell RNA-seq to measure gene activity in 8000 cells extracted at one time point from fruit fly embryos. About the same time, another team profiled gene activity of 50,000 cells from one larval stage of the nematode Caenorhabditis elegans. The data indicated which proteins, called transcription factors, were guiding the cells to differentiate into specialized types.


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