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. Author manuscript; available in PMC: 2024 Feb 3.
Published in final edited form as: Nat Cancer. 2023 Aug 3;4(8):1063–1082. doi: 10.1038/s43018-023-00595-y

Figure 2. Defining cancer stem cells and their niche.

Figure 2

(A) Functional strategies to identify CSCs include: (i) transplantation assays (tumor subpopulations isolated by fluorescence-activated cell sorting are transplanted into immunodeficient mice. If CSCs are grafted, a tumor will appear and will recapitulate tumor heterogeneity, while non-CSCs will be less efficient to propagate the tumor following transplantation), (ii) lineage tracing of CSCs (which allows to follow their fate during tumor progression and to assess clonal expansion) and (iii) lineage ablation (which allows the elimination of a specific subpopulation. If CSCs are eliminated, the remaining subpopulations will not be able to sustain tumor growth, and tumor regression will occur). (B) A crosstalk between CSCs and their microenvironment is essential to sustain tumor growth. CSCs are supported by a niche composed by cancer-associated fibroblasts, endothelial cells and immune cells, which extrinsically promote tumor stemness. CAF, cancer-associated fibroblast; CSC, cancer stem cell; EC, endothelial cell; FACS, fluorescence-activated cell sorting; TAM, tumor-associated macrophage.