Amélie Roehrig, Theo Z Hirsch, Aurore Pire, Guillaume Morcrette, Barkha Gupta, Charles Marcaillou, Sandrine Imbeaud, Christophe Chardot, Emmanuel Gonzales, Emmanuel Jacquemin, Masahiro Sekiguchi, Junko Takita, Genta Nagae, Eiso Hiyama, Florent Guérin, Monique Fabre, Isabelle Aerts, Sophie Taque, Véronique Laithier, Sophie Branchereau, Catherine Guettier, Laurence Brugières, Brice Fresneau, Jessica Zucman-Rossi, Eric Letouzé
Hepatoblastomas (HB) display heterogeneous cellular phenotypes that influence the clinical outcome, but the underlying mechanisms are poorly understood. Here, we use a single-cell multiomic strategy to unravel the molecular determinants of this plasticity. We identify a continuum of HB cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activations underlying cell state transitions...
April 8, 2024: Nature Communications