Etienne Gontier, Jean Ripoche, Kathleen Flosseau, Sophie Branchereau, Stefano Cairo, Alexandre Labedade, Marc Bevilacqua, Baudouin Denis de Senneville, Christophe Grosset, Christophe Chardot, Fatma Zohra Khoubai, Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Modélisation Mathématique pour l'Oncologie (MONC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux Imaging Center (BIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut François Magendie-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Chercheur indépendant, XenTech [Evry], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université de Bordeaux (UB), This work was supported by the charity Eva pour la Vie, La Fondation ARC pour la Recherche sur le Cancer (contract N° PJA 20191209631), La Région Nouvelle-Aquitaine, La Fondation Groupama pour la Santé and Groupama Centre-Atlantique. Microscopy Imaging was performed at the Bordeaux Imaging Centre, which is a member of the FranceBioImaging national infrastructure (ANR-10-INBS-04)., ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto di Ricerca Pediatrica [Padova, Italy] (IRP), Hôpital Bicêtre, Istituto di Ricerca Pediatrica Città della Speranza, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM), PlaFRIM (https://www.plafrim.fr), and Grosset, Christophe
Despite recent progress in the characterization of tumour components, the tri-dimensional (3D) organization of this pathological tissue and the parameters determining its internal architecture remain elusive. Here, we analysed the spatial organization of patient-derived xenograft tissues generated from hepatoblastoma, the most frequent childhood liver tumour, by serial block-face scanning electron microscopy using an integrated workflow combining 3D imaging, manual and machine learning-based semi-automatic segmentations, mathematics and infographics. By digitally reconstituting an entire hepatoblastoma sample with a blood capillary, a bile canaliculus-like structure, hundreds of tumour cells and their main organelles (e.g. cytoplasm, nucleus, mitochondria), we report unique 3D ultrastructural data about the organization of tumour tissue. We found that the size of hepatoblastoma cells correlates with the size of their nucleus, cytoplasm and mitochondrial mass. We also found anatomical connections between the blood capillary and the planar alignment and size of tumour cells in their 3D milieu. Finally, a set of tumour cells polarized in the direction of a hot spot corresponding to a bile canaliculus-like structure. In conclusion, this pilot study allowed the identification of bioarchitectural parameters that shape the internal and spatial organization of tumours, thus paving the way for future investigations in the emerging onconanotomy field., de Senneville et al. demonstrate an integrated workflow combining 3D imaging, manual and machine learning-based semi-automatic segmentation, mathematics and infographics to study the spatial organization of patient-derived hepatoblastoma xenograft tissues. Their approach potentially assists investigations of this childhood liver tumour and other types of tumour tissues.