PMID_29988129

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Dataset ID PMID_29988129
Abstract Cancer cells are embedded in the tumor microenvironment (TME), a complex ecosystem of stromal cells. Here, we present a 52,698-cell catalog of the TME transcriptome in human lung tumors at single-cell resolution, validated in independent samples where 40,250 additional cells were sequenced. By comparing with matching non-malignant lung samples, we reveal a highly complex TME that profoundly molds stromal cells. We identify 52 stromal cell subtypes, including novel subpopulations in cell types hitherto considered to be homogeneous, as well as transcription factors underlying their heterogeneity. For instance, we discover fibroblasts expressing different collagen sets, endothelial cells downregulating immune cell homing and genes coregulated with established immune checkpoint transcripts and correlating with T-cell activity. By assessing marker genes for these cell subtypes in bulk RNA-sequencing data from 1,572 patients, we illustrate how these correlate with survival, while immunohistochemistry for selected markers validates them as separate cellular entities in an independent series of lung tumors. Hence, in providing a comprehensive catalog of stromal cells types and by characterizing their phenotype and co-optive behavior, this resource provides deeper insights into lung cancer biology that will be helpful in advancing lung cancer diagnosis and therapy.
Description Phenotype molding of stromal cells in the lung tumor microenvironment
Number of cells 52547
Number of genes 24078
Number of samples 19
Curated Organism Homo Sapiens
Curated Tissue Lung
Curated Disease Carcinoma, Non-Small-Cell Lung; Pulmonary Disease, Chronic Obstructive
Curated Cell Lines None
Curated Cell Type Pneumocyte, Epithelial Cell, Myeloid Cell, Fibroblast, Endothelial Cell, Neoplastic Cell, T Cell, B Cell
Curated Drug None
Marker genes for cell type are available True
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