Spatial multiomics reveals a subpopulation of fibroblasts associated with cancer stemness in human hepatocellular carcinoma
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Le résumé fourni par la source
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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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Spatial multiomics reveals a subpopulation of fibroblasts associated with cancer stemness in human hepatocellular carcinoma
- Date Crossref
- 13/08/2024
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Shanghai Institute of Nutrition and Health pays non établi dans la noticeStructure de recherche
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University of Chinese Academy of Sciences CAS Key Laboratory of Computational Biology pays non établi dans la noticeUniversité ou école supérieure
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Xuzhou Medical College pays non établi dans la noticeUniversité ou école supérieure
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Second Military Medical University pays non établi dans la noticeUniversité ou école supérieure
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Eastern Hepatobiliary Surgery Hospital Department of Pathology pays non établi dans la noticeÉtablissement de santé
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Ministry of Education of the People's Republic of China pays non établi dans la noticeOrganisme public
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Xuzhou Medical University Cancer Institute pays non établi dans la noticeUniversité ou école supérieure
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Molecular Pathology Laboratory pays non établi dans la noticeStructure de recherche
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Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer pays non établi dans la noticeStructure de recherche
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National Center for Liver Cancer and International Cooperation Laboratory On Signal Transduction pays non établi dans la noticeStructure de recherche
Shanghai Institute of Nutrition and Health, CAS Key Laboratory of Computational Biology — University of Chinese Academy of Sciences et Xuzhou Medical College, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.