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

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Davidson , S , Efremova , M , Riedel , A , Mahata , B , Pramanik , J , Huuhtanen , J , Kar , G , Vento-Tormo , R , Hagai , T , Chen , X , Haniffa , M A , Shields , J D & Teichmann , S A 2020 , ' Single-Cell RNA Sequencing Reveals a Dynamic Stromal Niche That Supports Tumor Growth ' , Cell Reports , vol. 31 , no. 7 , 107628 . https://doi.org/10.1016/j.celrep.2020.107628

Title: Single-Cell RNA Sequencing Reveals a Dynamic Stromal Niche That Supports Tumor Growth
Author: Davidson, Sarah; Efremova, Mirjana; Riedel, Angela; Mahata, Bidesh; Pramanik, Jhuma; Huuhtanen, Jani; Kar, Gozde; Vento-Tormo, Roser; Hagai, Tzachi; Chen, Xi; Haniffa, Muzlifah A.; Shields, Jacqueline D.; Teichmann, Sarah A.
Contributor: University of Helsinki, Department of Clinical Chemistry and Hematology
Date: 2020-05-19
Language: eng
Number of pages: 24
Belongs to series: Cell Reports
ISSN: 2211-1247
URI: http://hdl.handle.net/10138/316207
Abstract: 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.
Subject: ANTITUMOR IMMUNE-RESPONSE
C3A RECEPTOR
EXTRACELLULAR-MATRIX
FACTOR-BETA
CANCER
FIBROBLASTS
MICROENVIRONMENT
MYOFIBROBLASTS
HETEROGENEITY
SAFETY
1182 Biochemistry, cell and molecular biology
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