Spatial multiomics reveals a subpopulation of fibroblasts associated with cancer stemness in human hepatocellular carcinoma.

IF 10.4 1区 生物学 Q1 GENETICS & HEREDITY Genome Medicine Pub Date : 2024-08-13 DOI:10.1186/s13073-024-01367-8
Si-Yu Jing, Dan Liu, Na Feng, Hui Dong, He-Qi Wang, Xi Yan, Xu-Feng Chen, Min-Cheng Qu, Ping Lin, Bin Yi, Feiling Feng, Lei Chen, Hong-Yang Wang, Hong Li, Yu-Fei He
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Abstract

Background: Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear.

Methods: We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays.

Results: We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells.

Conclusions: We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.

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空间多组学揭示了人肝细胞癌中与癌症干细胞相关的成纤维细胞亚群。
背景:癌症相关成纤维细胞(CAFs)是肿瘤微环境(TME)中的主要细胞类型,在各种肿瘤中都发现了CAF亚群。然而,CAF如何在空间上协调肝脏微环境中的其他细胞群以促进癌症进展仍不清楚:我们结合了多区域蛋白质组学(6 位患者,24 个样本)、10X Genomics Visium 空间转录组学(11 位患者,25 个样本)和多重成像(92 位患者,264 个样本)技术,来解读成纤维细胞的表达异质性、功能多样性、空间分布、共定位和相互作用。从5名肝癌患者体内分离的细胞和体外功能测试验证了新发现的CAF亚群:结果:我们发现了一个以 COL1A2、COL4A1、COL4A2、CTGF 和 FSTL1 的表达为标志的肝脏 CAF 亚群,并将其命名为 F5-CAF。F5-CAF优先位于肿瘤巢内和周围,并与肝细胞癌(HCC)中干性较强的癌细胞共聚焦。对92名患者进行的多重染色和对371名患者进行的大量转录组研究表明,HCC中F5-CAF的丰度与预后恶化有关。进一步的体外实验表明,从肝癌患者体内分离出的F5-CAFs可促进HCC细胞的增殖和干性:我们发现了肝癌中的 CAF 亚群 F5-CAF,它与癌症干性和不良预后有关。我们的研究结果提供了潜在的机制,即TME中的CAF亚群通过支持癌症干细胞的存活来促进肝癌的发展。
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来源期刊
Genome Medicine
Genome Medicine GENETICS & HEREDITY-
CiteScore
20.80
自引率
0.80%
发文量
128
审稿时长
6-12 weeks
期刊介绍: Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.
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