Deciphering tumour tissue organization by 3D electron microscopy and machine learning.

Deciphering tumour tissue organization by 3D electron microscopy and machine learning.
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DOI:
10.1038/s42003-021-02919-z
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发表时间:
2021-12-13
影响因子:
5.9
通讯作者:
Grosset CF
Grosset CF
中科院分区:
生物学2区
文献类型:
--
作者:
de Senneville BD;Khoubai FZ;Bevilacqua M;Labedade A;Flosseau K;Chardot C;Branchereau S;Ripoche J;Cairo S;Gontier E;Grosset CF

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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.
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