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Updated: Sep 3, 2025
06:29
Microfluidic Co-culture of Renal Healthy and Tumor Epithelium to Model Kidney Cancer Progression
Published on: January 31, 2025
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Single-cell transcriptomes underscore genetically distinct tumor characteristics and microenvironment for hereditary
Ryosuke Jikuya1,2, Koichi Murakami3,4, Akira Nishiyama3
1Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
Iscience
|July 25, 2022
Summary
This study reveals how hereditary kidney cancers adapt to their microenvironment using single-cell analysis. Findings highlight distinct cellular origins and immune evasion strategies in cancers like HLRCC and BHD.
Area of Science:
- Oncology
- Genetics
- Cell Biology
Background:
- Understanding hereditary kidney cancer adaptation to the tumor microenvironment is crucial but incomplete.
- Hereditary kidney cancers arise from distinct cell types and exhibit unique microenvironmental interactions.
Purpose of the Study:
- To analyze single-cell transcriptomes from six hereditary kidney cancers.
- To characterize the cellular origins and tissue microenvironment adaptations of these cancers.
Main Methods:
- Single-cell RNA sequencing of 108,342 cells from patient specimens.
- Transcriptomic analysis to identify cell-of-origin characteristics and microenvironment features.
Main Results:
- Distinct transcriptomic profiles were observed for each hereditary kidney cancer type.
- Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated kidney cancer showed proximal tubule characteristics, lost in metastases, with suppressed T cells and TREM2-high macrophages promoting immune tolerance.
- Birt-Hogg-Dubé (BHD)-associated kidney cancer displayed intratumor heterogeneity and features of collecting duct intercalated cells, with FOXI1 gene upregulation.
Conclusions:
- Hereditary kidney cancers exhibit unique adaptations to their tissue microenvironment.
- These adaptations influence tumor behavior, including immune evasion and differentiation pathways.
- The study provides insights into the complex interplay between hereditary kidney cancers and their surroundings.
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