CRM External Seminar: Barbara Treutlein, Group leader, ETH Zurich, Quantitative Developmental Biology Lab, Zurich

Talk title

Understanding brain development and regeneration with single cell technologies

Host

Ian Chambers

Abstract

The brain is a highly complex and fascinating organ and we are interested in understanding how cellular heterogeneity emerges during brain development and how brain cells can regenerate upon injury. We are tackling these questions by applying and further developing integrative, multi-modal single-cell technologies.

In the first part of my talk, I will present our work on human pluripotent stem cell (PSC) derived organoids that model human brain development in vitro. We generated a data set of paired single-cell transcriptome and accessible chromatin profiling over a dense time course of human brain organoid development, which we utilized to infer a gene regulatory network of human brain organoid development. We then used pooled genetic perturbation with single-cell transcriptome readout to assess transcription factor requirement for cell fate and state regulation in organoid and identified an important role of GLI3 during human telencephalon dorso-ventral patterning. Further, we have developed single-cell methodologies to directly track developmental lineages in brain organoids and could identify clonality of brain organoid regions as well as a temporal window of regional fate specification. Finally, we are working towards engineering diverse human neuronal populations in vitro using morphogen screening approaches.

In the second part of my talk, I will present our work on understanding the organization and regeneration of the telencephalon in the axolotl salamander using single-cell genomics. We first generated a single-cell multiomic atlas of the axolotl telencephalon, identified evolutionary conservation of neuronal cell types and reconstructed trajectories of post-embryonic neurogenesis. We then showed that upon major injury, all neuronal cell types reemerge through regenerative neurogenesis and neuronal projections to other brain regions are re-established. Finally, we identified a regeneration specific state of neural progenitor cells that is characterized by expression of wound healing genes.

Together, our work highlights the power of single-cell technologies to understand the gene regulatory logic underlying brain development and regeneration.

Bio

Barbara Treutlein performed her PhD in single-molecule biophysics at LMU Munich, Germany. During her Postdoc with Stephen Quake at Stanford University, she pioneered the use of microfluidic-based single-cell transcriptomics to dissect the cellular composition of complex tissues, and to elucidate differentiation pathways during organ development and cell reprogramming. 2015-2018, she was a Max Planck Research Group Leader in Leipzig and held a tenure-track assistant professorship at TU Munich. Since 2019, Barbara is Professor for Quantitative Developmental Biology at the ETH Zürich Department of Biosystems Science and Engineering in Basel, Switzerland. Her group has pioneered the use of single-cell genomics and imaging approaches in combination with stem cell based 2- and 3-dimensional culture systems to study human organ development and regeneration. For her work, Barbara has received multiple awards including the Friedmund Neumann Prize of the Schering Foundation, the Dr. Susan Lim Award for Outstanding Young Investigator of the International Society for Stem Cell Research, the Young Investigator Award of the German Stem Cell Network, the Friedrich Miescher Award and the Cloetta Jubilee Prize. In 2019, Barbara became an EMBO Young Investigator and in 2022 was elected a member of EMBO.