Event:

For Phd-Stundents: Lunch (Sandwiches) at 12:30 with Barbara Treutlein

Recent advances in the field of stem cell biology have made it possible to model human developmental processes in vitro. We combine stem cell based in vitro systems with single-cell transcriptomics analysis to reconstruct human organ development. In my talk I will present our efforts on reconstructing neurogenesis during two biological scenarios.
The first part focuses on cerebral organoids, three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells. We use single-cell RNA-seq to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex in order to find out how well these in vitro systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo. We identify cells in the cerebral organoids that derived from regions resembling the fetal neocortex and find that these cells use gene expression programs remarkably similar to those of the fetal tissue. Covariance network analysis reveals known and novel interactions among transcriptional regulators central to neural progenitor proliferation and neuronal differentiation. Interestingly, among these transcriptional regulators are genes that have been shown to have the capacity to convert the fate of a non-neuronal somatic cell into a neuronal cell.
The second part focuses on direct reprogramming of mouse embryonic fibroblasts to induced neuronal cells. Using single-cell RNA-seq to deconstruct heterogeneity at time points along the reprogramming path, we were able to reconstruct the reprogramming path to induced neuronal cells and at the same time identify a competing myogenic program that emerges when using a single transcription factor but is repressed by a combination of factors.
In summary, these data provide a high-resolution approach for understanding transcriptome states during neuronal lineage differentiation and self-organization.