Alexander van Oudenaarden

Prof. dr. ir. Alexander van Oudenaarden

Hubrecht Institute-KNAW, University Medical Center Utrecht & Utrecht University

Prof. dr. ir. Alexander van Oudenaarden is director and group leader at the Hubrecht Institute (KNAW) and professor of quantitative biology of gene regulation at the Faculty of Science and the Faculty of Medicine at Utrecht University. His research group works with advanced (light) microscopy and sequencing technologies in order to study individual cells. Van Oudenaarden studied materials science and physics at Delft, where he also obtained his PhD in solid state physics. As a postdoc he worked at Stanford University collaborating with Steven Boxer and Julie Theriot. He was professor of physics and biology at the Massachusetts Institute of Technology (MIT). In 2012 he moved to the Hubrecht Institute after 15 years in the USA. His group combines techniques – in part developed by themselves – from developmental biology, molecular biology, physics, mathematics and computer science. He was awarded the 2011 and 2016 ERC Advanced Investigator grant and in 2017 van Oudenaarden won the Spinoza Award.

Title: Whole-organism clone-tracing using single-cell sequencing

Embryonic development is one of the most crucial periods in the life of a multicellular organism. A limited set of embryonic progenitors gives rise to all cells in the adult body. Determining which fate these progenitors acquire in adult tissue is a major challenge and requires the simultaneous measurement of clonal history and cell-type at single-cell resolution. Clonal history has traditionally been quantified by microscopically tracking cells during development, monitoring the heritable expression of genetically encoded fluorescent proteins and, most recently, by utilizing next generation sequencing technology exploiting somatic mutations, transposon tagging, viral barcoding, and CRISPR/Cas9 genome editing strategies. Single-cell transcriptomics on the other hand, provides a powerful technology platform for cell-type classification in an unbiased manner. However, integrating both measurements for many single cells has been a major hurdle. Here, we present ScarTrace, a single-cell sequencing strategy that allows us to simultaneously quantify information on clonal history and cell type for thousands of single cells obtained from different organs from adult zebrafish. Using this approach we show that all blood cells in the kidney marrow arise from a small set of multipotent embryonic progenitors that give rise to all blood cell types. In contrast, we find that cells in the eyes, brain, and caudal tail fin arise from many embryonic progenitors, which are more restricted and produce specific cell types in the adult tissue. Next we use ScarTrace to explore when embryonic cells commit to forming either left or right organs using the eyes and brain as a model system. Lastly we monitor regeneration of the caudal tail fin and identify a subpopulation of resident macrophages that have a clonal origin that is distinct from other blood cell types. We envision that ScarTrace will have major applications in other experimental model systems to match embryonic clonal origin to adult cell-type to ultimately reconstruct how the adult body was built from a single cell.