Monday 6 June 2022 | 12:00 noon – ICGEB Trieste, ITALY

Anton Wutz’s lab, Epigenetic Regulation and Cell Identity Control Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, Zurich, SWITZERLAND

Super-resolution genetics in haploid stem cells: decoding Hedgehog signaling in development and cancer

(Host: V. Venturi)

Host: V. Venturi

Advances in the generation of haploid embryonic stem cells (ESCs), capable of self-renewal and differentiation, have laid the groundwork for numerous biomedical applications in developmental biology and reproductive medicine. Haploid cells possess one copy of each gene, facilitating the generation of loss-of-function mutations in a single step and allowing the development of efficient functional genomic strategies. Our group was the first to derive mammalian haploid embryonic stem cells and profoundly contributed to explore their developmental potential. In these years, the methodology reached a maturity that allows us to challenge complex phenotypes with a sensitivity unreachable with any other screening approach. Using this cellular system, we explored the role of the Hedgehog (HH) pathway during the development and diseases. We used genetic screens in haploid ESCs to identify novel modulators of the HH pathway and we discovered an unexplored function of the Golgi compartment in signaling activation.

Additionally, we aim to understand the molecular events leading to HH signaling deregulation in multiple tumors. For this purpose, we take advantage of the plasticity of haploid ESCs to generate tumor models reflecting the earliest events of cellular transformation. Deep mutagenesis of their haploid genome will allow us to detect so far missed connections unveiling oncogenic induced lethal interactions highly relevant for the development of new cancer therapies.