2nd MLFPM Summer School: Barbara Treutlein
Channel: MLFPM ITN
Date: 2020-11-30

Second Summer School "Machine Learning Frontiers in Precision Medicine", September 21-23, 2020

Barbara Treutlein (ETH Zürich): Organ development and regeneration through the lens of single-cell genomics

Recent advances in stem cell biology have made it possible to grow in vitro three-dimensional human organoids that model human brain development. We are using these organoid systems in combination with single-cell genomic methods to understand molecular mechanisms underlying fate decisions during human brain development, to explore the mechanisms underlying developmental disorders, and to identify features of organ development that are uniquely human. We deconstruct cellular composition and reconstruct differentiation trajectories over the entire course of human cerebral organoid development from pluripotency, through neuroectoderm and neuroepithelial stages, followed by divergence into neuronal fates within the dorsal and ventral forebrain, as well as midbrain and hindbrain regions. We find that the gene expression patterns in the human organoid forebrain are reproducible across iPSC lines from different individuals. We use lineage recording based on single-cell transcriptome-coupled lineage tracing, nuclei tracking from long-term light sheet microscopy, and spatial transcriptomics to understand lineage commitment and dynamics during cerebral organoid regionalization. We use single-cell CRISPR perturbation screens to identify the relevance of genes for cell fate decisions. Finally, we compare human and chimpanzee cerebral organoid development at the single-cell level to identity features that are specific to humans. Altogether, the combination of organoid technologies and single-cell technologies enable unprecedented insight into human development.

The summer school is part of the H2020 Marie Curie Innovative Training Network "Machine Learning Frontiers in Precision Medicine" (https://mlfpm.eu). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 813533.