Single-cell sequencing explores higher-order achievements in brain development

Cranial neural crest cells, referred to as CNCCs
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These extraordinary stem cells not only form most of the skull and facial bones of all vertebrates, from fish to humans, but also give rise to everything from the gills to the cornea

"The incredible diversity of cell types that CNCCs can generate has long fascinated biologists
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By studying this process in the genetically controllable zebrafish, we have identified a number of potential switches that allow CNCCs to form these very different cell type," said Crump, professor of stem cell biology and regenerative medicine at the Keck School of Medicine of USC

Led by postdoc Peter Fabian and doctoral students Kuo-Chang Tseng, Mathi Thiruppathy and Claire Arata, the team of scientists permanently tagged CNCCs with red fluorescent protein to track which cell types came from throughout the zebrafish life cycle
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They then used a powerful method called "single-cell genomics" to identify the organization of the entire set of active genes and DNA from hundreds of thousands of individual CNCCs

Fabian said: "We created a computational analysis that we call 'constellations' because the final visual output of this technique is reminiscent of constellations in the sky
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Compared to astrology, our constellation algorithm does predict cells future and reveal key genes that may control cell development

Using this new bioinformatics approach, the team found that CNCCs do not initially have all the information needed to create the enormous diversity of cell types

"By conducting the most comprehensive single-cell study of vertebrate cell populations to date, we have not only gained important insights into vertebrate head development, but have also created a broad framework for studying the development and regeneration of organ systems throughout the body," Crump said.
Useful computational tool

Magazine

Nature Communications

DOI

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