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Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity.

Cancer cell (2021-07-24)
Colin Hutton, Felix Heider, Adrian Blanco-Gomez, Antonia Banyard, Alexander Kononov, Xiaohong Zhang, Saadia Karim, Viola Paulus-Hock, Dale Watt, Nina Steele, Samantha Kemp, Elizabeth K J Hogg, Joanna Kelly, Rene-Filip Jackstadt, Filipa Lopes, Matteo Menotti, Luke Chisholm, Angela Lamarca, Juan Valle, Owen J Sansom, Caroline Springer, Angeliki Malliri, Richard Marais, Marina Pasca di Magliano, Santiago Zelenay, Jennifer P Morton, Claus Jørgensen

Fibroblasts display extensive transcriptional heterogeneity, yet functional annotation and characterization of their heterocellular relationships remains incomplete. Using mass cytometry, we chart the stromal composition of 18 murine tissues and 5 spontaneous tumor models, with an emphasis on mesenchymal phenotypes. This analysis reveals extensive stromal heterogeneity across tissues and tumors, and identifies coordinated relationships between mesenchymal and immune cell subsets in pancreatic ductal adenocarcinoma. Expression of CD105 demarks two stable and functionally distinct pancreatic fibroblast lineages, which are also identified in murine and human healthy tissues and tumors. Whereas CD105-positive pancreatic fibroblasts are permissive for tumor growth in vivo, CD105-negative fibroblasts are highly tumor suppressive. This restrictive effect is entirely dependent on functional adaptive immunity. Collectively, these results reveal two functionally distinct pancreatic fibroblast lineages and highlight the importance of mesenchymal and immune cell interactions in restricting tumor growth.

Product Number
Product Description

Polyethylenimine hydrochloride, linear, average Mn 10,000, PDI ≤1.5
DNase I, grade II, from bovine pancreas
Heparin sodium salt from porcine intestinal mucosa, Grade I-A, ≥180 USP units/mg
Hyaluronidase from bovine testes, Type VIII, lyophilized powder, 300-1,000 U/mg
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Tamoxifen, ≥99%
Accutase® solution, sterile-filtered, suitable for cell culture
Anti-Actin, α-Smooth Muscle antibody, Mouse monoclonal, clone 1A4, purified from hybridoma cell culture
Puromycin dihydrochloride from Streptomyces alboniger, powder, BioReagent, suitable for cell culture
Bovine Serum Albumin, heat shock fraction, protease free, pH 7, ≥98%
Hexadimethrine bromide, ≥95%