A series of studies conducted by Alexander Schier, the Leo Erikson Life Sciences Professor of Molecular and Cellular Biology, and members of his lab, including Jeff Farrell, Yiqun Wang, Bushra Raj, and James Gagnon, and additional work by colleagues from Harvard Medical School (HMS), including Allon Klein, Sean Megason and Marc Kirschner, have been featured as the “2018 Breakthrough of the Year” by Science Magazine.
Using a combination of single-cell RNA sequencing and CRISPR-Cas9 genome editing, the team was able to mark and follow thousands of individual embryonic cells before turning to computational approaches to reconstruct the developmental trajectories and lineages that generate neurons, muscle, blood, and other cell types. The work was described in three papers published in Science in April and a paper in Nature Biotechnology in March.
“Science’s Breakthrough of the Year recognizes the application of this tag-analyze-assemble approach to one of the most fundamental and fascinating processes in biology — the seemingly miraculous transformation of single cells into complex organisms — providing rich information about cell-type inventories and laying the foundation for many future studies,” Science editor in chief Jeremy Berg wrote in announcing the recognition. “The large and rich datasets that have been generated, and the techniques that will produce more, constitute exciting breakthroughs in developmental biology.”
From a solitary cell emerges others that are needed to build an organism. Pictured is a Xenopus egg in one stage of dividing.
From one, many
Harvard scientists reveal the genetic roadmap to building an entire organism from a single cell
The research teams traced the fates of individual cells over the first day of an embryo’s life, and their analyses revealed the comprehensive landscape of which genes were switched on or off, and when, as embryonic cells transitioned into new cell states and types.
Together, the findings represent a catalog of genetic “recipes” for generating different cell types in two important model species and provide an unprecedented resource for the study of developmental biology and disease.
“With single-cell sequencing, we can, in a day’s work, recapitulate decades of painstaking research on the decisions cells make at the earliest stages of life,” said Klein, an assistant professor of systems biology at HMS. “With the approaches that we’ve developed, we’re charting what we think the future of developmental biology will be as it transforms into a quantitative, big-data-driven science.”
In addition to shedding new light on the early stages of life, the work could open the door to a new understanding of a host of diseases, said Schier.
“We foresee that any complex biological process in which cells change gene expression over time can be reconstructed using this approach,” he said. “Not just the development of embryos, but also the development of cancer or brain degeneration.”