ArticleNPJ precision oncology2024
Single-cell and spatial analyses revealed the co-location of cancer stem cells and SPP1+ macrophage in hypoxic region that determines the poor prognosis in hepatocellular carcinoma.
Article in NPJ precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Mapping the knowledge domains of literature on hepatocellular carcinoma and liver failure: a bibliometric approach.Frontiers in oncology · 2025Pooled it
- Spatial multi‑omics identifies an SPP1+ macrophage‑driven anti‑apoptotic niche in osteoarthritis synovium via the SPP1‑CD44 axis.International journal of molecular medicine · 2026Article
- Unraveling the tapestry: Lessons from multi-omics and spatial biology in hepatocellular cancer.Hepatology (Baltimore, Md.) · 2026Review
- Stemness plasticity in hepatocellular carcinoma: spatial niches and therapeutic implications.Journal of liver cancer · 2026Article
- scRNA-seq and bulk RNA-seq reveal the characteristics of macrophage copper metabolism and establish a risk signature in hepatocellular carcinoma.Translational cancer research · 2026Article
- Spatial multi omic profiling maps hypoxia-driven pro-fibrotic SPP1Experimental hematology & oncology · 2026Article
- Identification of a distinct cluster of LY6EBritish journal of cancer · 2026Article
- Copper homeostasis and cuproptosis: molecular mechanisms and therapeutic opportunities.Molecular biomedicine · 2026Review
- Review
- POSTN(+) fibroblasts and SPP1(+) macrophages in scar formation: A review of mechanisms and therapeutic targets (Review).Molecular medicine reports · 2026Review
- Spatial co-expression and cell-cell communication inference from spatially resolved transcriptomics with CONCISE.bioRxiv : the preprint server for biology · 2026Article
- Late-stage dedifferentiation and epigenetic memory of cancer stem cells in hepatocellular carcinoma.Journal of translational medicine · 2026Article
- Single-Cell Transcriptomic Profiling Reveals Immunometabolic Reprogramming and Cell-Cell Communication in the Tumor Microenvironment of Human Hepatocellular Carcinoma.International journal of molecular sciences · 2026Article
- Dissecting the Transcriptomic Profile of CD163Liver cancer · 2026Article
- Understanding how hypoxia contributes to liver cancer stem cells maintenance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Spatial single-cell landscape of tumor-associated macrophages and their crosstalk with the tumor microenvironment.Cell discovery · 2026Article
- Review
- Review
- scSurvival: Single-Cell Survival Analysis of Clinical Cancer Cohort Data at Cellular Resolution.Cancer discovery · 2026Article
- Single-Cell Transcriptomics Reveals Immune Modulation by Telmisartan in Colorectal Cancer.Cells · 2026Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In hepatocellular carcinoma (HCC), classical cancer stem cells (CSC) markers were shared by normal stem cells, targeting which may hinder hepatic regeneration and cause liver failure. Additionally, the spatial structure of CSC still remained elusive. To address these limitations, we undertook a comprehensive study combining single-cell data (56,022 cells from 20 samples) and spatial data (38,191 spots from eight samples) to obtain CSC signature and uncover its spatial structure. Utilizing the CytoTRACE algorithm, we discretely identified CSC, which displayed upregulated proliferation pathways regulated by HIF1A. A CSC signature of 107 genes was then developed using Weighted Gene Co-expression Network Analysis (WGCNA). Notably, HCC patients with high CSC levels exhibited an accumulation of SPP1+ macrophages (Macro_SPP1) expressing metalloproteinases (MMP9, MMP12, and MMP7) regulated by HIF1A, suggesting a hypoxic tumor region connecting Macro_SPP1 and CSC. Both CSC and Macro_SPP1 correlated with worse prognosis and undesirable immunotherapy response. Spatial analysis revealed the co-location of CSC and Macro_SPP1, with CD8 T cells excluded from the tumor region. The co-location area and non-tumor area of boundary exhibited a high level of hypoxia, with the HAVRC2 checkpoint highly expressed. Within the co-location area, the SPP1 signaling pathway was most active in cell-cell communication, with SPP1-CD44 and SPP1-ITGA/ITGB identified as the main ligand-receptor pairs. This study successfully constructed a CSC signature and demonstrated the co-location of CSC and Macro_SPP1 in a hypoxic region that exacerbates the tumor microenvironment in HCC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.