Virtual Lecture Series
‘Recent Advances in Single Cell Omics’:
55. Céline Vallot (Institut Curie)

The dynamic nature of chromatin and transcriptional features are expected to participate to tumor evolution. Our group focuses on the study of the dynamics of histone modifications in cancer cells upon cancer treatment as well as during the initial steps of tumorigenesis. We develop experimental and computational approaches to map histone marks at single-cell resolution, enabling the investigation of the dynamics of chromatin marks in tumor samples (Grosselin et al. Nat Genet 2019; Prompsy et al. Nat Comm 2020).
We have recently combined single-cell epigenomic and transcriptomic approaches to lineage tracing strategies to reveal the initial epigenomic events driving tolerance to chemotherapy in triple-negative breast cancer (Marsolier & Prompsy et al., Nat Genet 2022). We show that the repressive histone mark H3K27me3 is a lock to the activation of a drug-persistent expression program in breast cancers. Under chemotherapy, very few cells can survive the treatment, and these cells have a remodeled repressive epigenome, with targeted loss at key promoters. Using demethylase inhibitor in combination to chemotherapy, we improve the response rate and delay recurrence both in vitro and in vivo.
We also study mechanisms of cell plasticity in early breast tumorigenesis in vivo. We have recently mapped state transitions during Brca1-tumorigenesis in the mouse. We discovered that luminal progenitor cells undergo a partial epithelial to mesenchymal transition at the onset of tumorigenesis (Landragin &Saichi, unpublished 2022).