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Advanced Science | 单细胞+空间转录组定位 NSCLC 耐药生态位

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TL;DR - A study combining single-cell and spatial transcriptomics identifies a therapy-resistant NSCLC niche where DSG2⁺ cancer stem cells co-localize with FAP⁺ myofibroblastic CAFs at tumor boundaries. The niche is associated with poorer chemotherapy, EGFR-TKI, and immunotherapy outcomes.

  • A reproducible 127-gene cancer stem-cell signature identified DSG2 as its strongest marker.
  • Spatial transcriptomics and multiplex immunofluorescence localized DSG2⁺ stem-like cells alongside FAP⁺ myCAFs at tumor borders.
  • CellChat implicated MDK–NCL signaling, while co-culture experiments showed myCAFs enhance stemness through an MMP-dependent mechanism.
  • DSG2 knockdown reduced stemness markers, self-renewal, invasion, and proliferation in NSCLC cell lines.

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Advanced Science | 单细胞+空间转录组定位 NSCLC 耐药生态位

WeChat: 生信技能树 2026-07-21

TL;DR - A study combining single-cell and spatial transcriptomics identifies a therapy-resistant NSCLC niche where DSG2⁺ cancer stem cells co-localize with FAP⁺ myofibroblastic CAFs at tumor boundaries. The niche is associated with poorer chemotherapy, EGFR-TKI, and immunotherapy outcomes.

  • A reproducible 127-gene cancer stem-cell signature identified DSG2 as its strongest marker.
  • Spatial transcriptomics and multiplex immunofluorescence localized DSG2⁺ stem-like cells alongside FAP⁺ myCAFs at tumor borders.
  • CellChat implicated MDK–NCL signaling, while co-culture experiments showed myCAFs enhance stemness through an MMP-dependent mechanism.
  • DSG2 knockdown reduced stemness markers, self-renewal, invasion, and proliferation in NSCLC cell lines.
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