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An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity.

ABSTRACT: Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug sensitivities. Using single cell RNA-sequencing and high resolution 3D imaging, we further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like cells. Our organoid biobank captures the heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterised models for basic cancer research, drug-screening and personalised medicine.

SUBMITTER: Calandrini C

PROVIDER: S-EPMC7066173 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity.

Calandrini Camilla C Schutgens Frans F Oka Rurika R Margaritis Thanasis T Candelli Tito T Mathijsen Luka L Ammerlaan Carola C van Ineveld Ravian L RL Derakhshan Sepide S de Haan Sanne S Dolman Emmy E Lijnzaad Philip P Custers Lars L Begthel Harry H Kerstens Hindrik H D HHD Visser Lindy L LL Rookmaaker Maarten M Verhaar Marianne M Tytgat Godelieve A M GAM Kemmeren Patrick P de Krijger Ronald R RR Al-Saadi Reem R Pritchard-Jones Kathy K Kool Marcel M Rios Anne C AC van den Heuvel-Eibrink Marry M MM Molenaar Jan J JJ van Boxtel Ruben R Holstege Frank C P FCP Clevers Hans H Drost Jarno J

Nature communications 20200311 1

Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, rena ...[more]

PMID: 32161258

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Project description:Macrophages are dynamic immune cells that govern both normal tissue function and disease progression. However, standard methods to measure heterogeneity in macrophage function within tissues require tissue excision and fixation, which limits our understanding of diverse macrophage function in vivo. Two-photon microscopy of the endogenous metabolic co-enzymes NAD(P)H and flavin adenine dinucleotide (FAD) (metabolic autofluorescence imaging) enables dynamic imaging of mouse models in vivo. Here, we demonstrate metabolic autofluorescence imaging to assess cell-level macrophage heterogeneity in response to normal and cancerous tissue microenvironments in vivo. NAD(P)H and FAD fluorescence intensities and lifetimes were measured for both tissue-resident macrophages in mouse ear dermis and tumor-associated macrophages in pancreatic flank tumors. Metabolic and spatial organization of macrophages were determined by performing metabolic autofluorescence imaging and single macrophage segmentation in mice engineered for macrophage-specific fluorescent protein expression. Tumor-associated macrophages exhibited decreased optical redox ratio [NAD(P)H divided by FAD intensity] compared to dermal macrophages, indicating that tumor-associated macrophages are more oxidized than dermal macrophages. The mean fluorescence lifetimes of NAD(P)H and FAD were longer in dermal macrophages than in tumor-associated macrophages, which reflects changes in NAD(P)H and FAD protein-binding activities. Dermal macrophages had greater heterogeneity in optical redox ratio, NAD(P)H mean lifetime, and FAD mean lifetime compared to tumor-associated macrophages. Similarly, standard markers of macrophage phenotype (CD206 and CD86) assessed by immunofluorescence revealed greater heterogeneity in dermal macrophages compared to tumor-associated macrophages. Ultimately, metabolic autofluorescence imaging provides a novel tool to assess tissue-specific macrophage behavior and cell-level heterogeneity in vivo in animal models.

Dataset Information

An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity.

Publications

An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity.

Similar Datasets

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