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Fig. 1 | Molecular Cancer

Fig. 1

From: Tumorigenic circulating tumor cells from xenograft mouse models of non-metastatic NSCLC patients reveal distinct single cell heterogeneity and drug responses

Fig. 1

Liquid biopsy CDX mouse model generation and single cell sequencing analyses. A Upper panels: Surgically resected NSCLC primary tumor fragments were implanted into NSG mice to develop ptPDXs. Images of ptPDX tumor-bearing mice at euthanasia (with patient IDs) showing the subcutaneous tumors; Scale bar, 1 cm. Lower panels: Blood was collected from ptPDX mice at the time of euthanasia and CTCs enriched. Human CTCs were confirmed by immunostaining using anti-human Pan-CK (FITC), hCD45 (DSRed) and mCD45 (Cy5) with DAPI for nuclei identification; Scale bar, 20 μm. B Development of CDX mouse models from non-metastatic NSCLC patients: Representative images of the two NSCLC patients’ CT (MU150) and PET/CT (MU197) imaging showing primary tumors (red arrows) that led to CDX model development following s.c. reimplantation of ptPDX-CTCs into naĂ¯ve NSG mice. Images of subcutaneous CDX tumors (dotted circles) are shown. Insets: Excised tumors. Scale bar, 1 cm. C Single nuclear (sn)RNA-seq transcriptome landscape of MU150 ptPDX, MU150 CDX, MU197 ptPDX and MU197 CDX visualized by uniform manifold approximation and projection (UMAP) (upper panels). Middle panels: Feature plots of SFTPB with dotted circles highlighting the AT2-like clusters (zoomed insets). Lower panels: Heat maps of AT2 cell type canonical markers using differentially expressed genes (DEGs) of all clusters of all samples confirming the existence of additional AT2-like cluster in CDX tumors. Dotted lines highlight AT2 clusters. Cell type canonical markers are provided in supplementary file 2. D An external single cell sequencing data set of non-xenografted human NSCLC tumor tissues (eight primary tumors and five metastases) [10] was analyzed to validate single cell sequencing findings observed in ptPDX/CDX models. Upper panels: Single cell transcriptome landscape of human primary tumor (left) and metastases (right) tissues are visualized by UMAP. Middle panels: Feature plots of SFTPB with dotted circles highlighting the AT2-like clusters in primary tumor (left) and metastases (right) tissues. Lower panels: Heat maps of AT2 cell type canonical markers using differentially expressed genes (DEGs) of all clusters of primary tumors (left) and metastases (right) tissues. Dotted lines highlight AT2 clusters

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Molecular Cancer

ISSN: 1476-4598