Fig. 7. Possible pathways of communication between prostate tuft cells and their environment based on gene expression data.
Receptors or ligands that are enriched or specifically expressed in tuft cells were used to map cell-cell interactions in all datasets. A Cell-cell interactions between tuft cells and other populations in prostate cancer, highlighting the ligands expressed in all cell types that target receptors expressed in tuft cells. The size of the dot represents the interaction specificity defined by NATMI [69] as uniquely expressed by the interacting pair, while color represents expression magnitude defined by LRscore [70]. Absence of dots in the plots indicate that the interacting genes are expressed in the less than 10% of both cell populations. The top 20 interacting pairs for each dataset show that tuft cell receptors are mostly targeted by ligands expressed by fibroblasts and immune cells. B Cell-cell interactions, highlighting the ligands expressed by tuft cells targeting receptors on all cell types in the datasets. Only ligands that are enriched or specifically expressed in tuft cells are used to map interactions. The top 20 interacting pairs show that tuft cell ligands target immune cells in all datasets, but also endothelial and smooth muscle cells in PRN and PRT, and neuroendocrine cells in PRT and human cancer. C Expression of sensing receptors on tuft cells suggests their ability to respond to environmental cues. Both PRN and PRT tuft cells express genes that may drive pro-tumorigenic and immunosuppressive signaling. Tuft cells may signal to fibroblasts (Lipc-Lrp1), smooth muscle and endothelial cells (Jag/Dll-Notch, Bmp7-Eng and Agt-Adra2a), immune cells (Ceacam1-Havcr2, Mif-Cd44/Cd74, Mif-Cd74/Cxcr4, Il25-Il17rb and prostaglandin (PG)-Ptger4), and to other epithelial cell types including neuroendocrine cells through ACh signaling to different acetylcholine receptors (AChR). They also receive signals from other cell types through RTKs and Adra2a receptors. Figure 7C was created using BioRender.com.