Barbara Treutlein

Barbara Treutlein

ETH Zürich, Switzerland

Barbara Treutlein is an Associate Professor at the Department of Biosystems Science and Engineering of ETH Zürich in Basel. Her group uses and develops quantitative single-cell genomic approaches to understand the mechanisms underlying development, regeneration and reprogramming. In particular, they use stem cell derived human organoids to model the development of human organs in vitro and to understand how cell fate is orchestrated in complex human tissues. In recent years, her group have shown that cell composition, lineage relationships and gene networks controlling human cerebral and liver organoid development are remarkably similar to those in the developing human fetus. They are now manipulating these stem cell derived tissues and growing tissues from human patients with developmental disorders to find out how certain genes and gene networks contribute to the establishment of different cell lineages. They are also analyzing the cellular dynamics of early organoid development to identify when and where patterning emerges and lineages diverge. Further, the group has been using single-cell transcriptomics to understand mechanisms underlying the direct reprogramming of fibroblasts and pericytes into induced neuronal cells. Finally, the Treutlein group has been collaborating with Elly Tanaka’s lab to provide a molecular view of individual cells as they are regenerating an axolotl limb.

Title of talk : Human organoid development through the lens of single-cell technologies

Abstract

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. 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 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 multiomics measurements in combination with a new computational tool to reconstruct a gene regulatory network underlying fate decisions during early brain organoid development and use pooled genetic perturbation with single-cell transcriptome readout to assess transcription factor requirement for cell fate and state regulation in organoid. We find interesting alterations of abundance of cell fates in response to perturbations and show that our gene regulatory network is predictive of the observed changes. Altogether, the combination of organoid technologies and single-cell technologies enable unprecedented insight into human development.

Friday, Sep 9

11:00 - 12:30
Talk during Session 6 | Embryogenesis and animal evolution

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