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Publication : Single-Cell RNA Sequencing Reveals a Dynamic Stromal Niche That Supports Tumor Growth.

First Author  Davidson S Year  2020
Journal  Cell Rep Volume  31
Issue  7 Pages  107628
PubMed ID  32433953 Mgi Jnum  J:332445
Mgi Id  MGI:6714722 Doi  10.1016/j.celrep.2020.107628
Citation  Davidson S, et al. (2020) Single-Cell RNA Sequencing Reveals a Dynamic Stromal Niche That Supports Tumor Growth. Cell Rep 31(7):107628
abstractText  Here, using single-cell RNA sequencing, we examine the stromal compartment in murine melanoma and draining lymph nodes (LNs) at points across tumor development, providing data at http://www.teichlab.org/data/. Naive lymphocytes from LNs undergo activation and clonal expansion within the tumor, before PD1 and Lag3 expression, while tumor-associated myeloid cells promote the formation of a suppressive niche. We identify three temporally distinct stromal populations displaying unique functional signatures, conserved across mouse and human tumors. Whereas "immune" stromal cells are observed in early tumors, "contractile" cells become more prevalent at later time points. Complement component C3 is specifically expressed in the immune population. Its cleavage product C3a supports the recruitment of C3aR(+) macrophages, and perturbation of C3a and C3aR disrupts immune infiltration, slowing tumor growth. Our results highlight the power of scRNA-seq to identify complex interplays and increase stromal diversity as a tumor develops, revealing that stromal cells acquire the capacity to modulate immune landscapes from early disease.
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