单细胞转录组突出了遗传性肾癌在基因上截然不同的肿瘤特征和微环境。
Single-cell transcriptomes underscore genetically distinct tumor characteristics and microenvironment for hereditary kidney cancers.
作者信息
Jikuya Ryosuke, Murakami Koichi, Nishiyama Akira, Kato Ikuma, Furuya Mitsuko, Nakabayashi Jun, Ramilowski Jordan A, Hamanoue Haruka, Maejima Kazuhiro, Fujita Masashi, Mitome Taku, Ohtake Shinji, Noguchi Go, Kawaura Sachi, Odaka Hisakazu, Kawahara Takashi, Komeya Mitsuru, Shinoki Risa, Ueno Daiki, Ito Hiroki, Ito Yusuke, Muraoka Kentaro, Hayashi Narihiko, Kondo Keiichi, Nakaigawa Noboru, Hatano Koji, Baba Masaya, Suda Toshio, Kodama Tatsuhiko, Fujii Satoshi, Makiyama Kazuhide, Yao Masahiro, Shuch Brian M, Schmidt Laura S, Linehan W Marston, Nakagawa Hidewaki, Tamura Tomohiko, Hasumi Hisashi
机构信息
Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.
Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
出版信息
iScience. 2022 May 25;25(6):104463. doi: 10.1016/j.isci.2022.104463. eCollection 2022 Jun 17.
Our understanding of how each hereditary kidney cancer adapts to its tissue microenvironment is incomplete. Here, we present single-cell transcriptomes of 108,342 cells from patient specimens including from six hereditary kidney cancers. The transcriptomes displayed distinct characteristics of the cell of origin and unique tissue microenvironment for each hereditary kidney cancer. Of note, hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated kidney cancer retained some characteristics of proximal tubules, which were completely lost in lymph node metastases and present as an avascular tumor with suppressed T cells and TREM2-high macrophages, leading to immune tolerance. Birt-Hogg-Dubé (BHD)-associated kidney cancer exhibited transcriptomic intratumor heterogeneity (tITH) with increased characteristics of intercalated cells of the collecting duct and upregulation of FOXI1-driven genes, a critical transcription factor for collecting duct differentiation. These findings facilitate our understanding of how hereditary kidney cancers adapt to their tissue microenvironment.
我们对每种遗传性肾癌如何适应其组织微环境的理解并不完整。在此，我们展示了来自患者标本（包括六种遗传性肾癌）的108342个细胞的单细胞转录组。这些转录组显示了每种遗传性肾癌的独特起源细胞特征和独特组织微环境。值得注意的是，遗传性平滑肌瘤病和肾细胞癌（HLRCC）相关的肾癌保留了近端小管的一些特征，这些特征在淋巴结转移中完全丧失，并表现为无血管肿瘤，伴有T细胞受抑制和TREM2高表达的巨噬细胞，从而导致免疫耐受。Birt-Hogg-Dubé（BHD）相关的肾癌表现出转录组肿瘤内异质性（tITH），集合管闰细胞特征增加，且FOXI1驱动基因上调，FOXI1是集合管分化的关键转录因子。这些发现有助于我们理解遗传性肾癌如何适应其组织微环境。
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