A series of studies conducted by teams led by Harvard Medical School systems biologists Allon Klein, Marc Kirschner and Sean Megason, as well as the work of teams led by Alexander Schier at Harvard University in collaboration with Aviv Regev at the Broad Institute of MIT-Harvard, have been featured as part of the “2018 Breakthrough of the Year” by Science.
Using a combination of single-cell RNA sequencing and CRISPR-Cas9 genome editing, the teams marked and followed 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. More information about the research involved can be found here.
“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.”
The research teams traced the fates of individual cells over the first day of the life of an embryo, and their analyses reveal the comprehensive landscape of which genes are switched on or off, and when, as embryonic cells transition 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 Allon Klein, HMS assistant professor of systems biology. “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 Alexander Schier, the Leo Erikson Life Sciences Professor of Molecular and Cellular Biology at Harvard.
“We foresee that any complex biological process in which cells change gene expression over time can be reconstructed using this approach,” Schier said. “Not just the development of embryos but also the development of cancer or brain degeneration.”
Marc Kirschner is the HMS John Franklin Enders University Professor of Systems Biology, and Sean Megason is HMS associate professor of systems biology.
Image: Sean Megason and Frederique Ruf