TY - JOUR T1 - Identification of Cancer-Associated Fibroblasts in Glioblastoma and Defining Their Pro-tumoral Effects JF - bioRxiv DO - 10.1101/2021.05.08.443250 SP - 2021.05.08.443250 AU - Saket Jain AU - Jonathan W. Rick AU - Rushikesh Joshi AU - Angad Beniwal AU - Jordan Spatz AU - Alexander Chih-Chieh Chang AU - Alan T. Nguyen AU - Sweta Sudhir AU - Ankush Chandra AU - Alex Haddad AU - Harsh Wadhwa AU - Sumedh S. Shah AU - Serah Choi AU - Josie L. Hayes AU - Lin Wang AU - Garima Yagnik AU - Joseph F. Costello AU - Aaron Diaz AU - Manish K. Aghi Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/10/2021.05.08.443250.abstract N2 - Despite their identification in some cancers, pro-tumoral cancer-associated fibroblasts (CAFs) were presumed absent in glioblastoma given the lack of brain fibroblasts. Serial trypsinization of primary glioblastoma cultures yielded cells with CAF morphology, CAF transcriptomic profile, and mesenchymal lineage in single-cell RNA-seq. Glioblastoma CAFs were attracted to glioblastoma stem cells (GSCs) and CAFs enriched GSCs. We created a resource of inferred crosstalk by mapping expression of receptors to their cognate ligands, identifying PDGF-β and TGF-β as mediators of GSC effects on CAFs, and osteopontin and hepatocyte growth factor as mediators of CAF-induced GSC enrichment. Glioblastoma CAFs also induced M2 macrophage polarization by producing the EDA fibronectin variant. Glioblastoma CAFs were enriched in the subventricular zone which houses neural stem cells that produce GSCs. Including CAFs in GSC-derived xenografts induced in vivo growth. These findings are among the first to identify glioblastoma CAFs and their GSC interactions, making them an intriguing target.Competing Interest StatementThe authors have declared no competing interest. ER -