GSE131415
Constitutive activity of the cation channel TRPM8 regulates the function and differentiation of human monocytes
This study investigated the impact of TRPM8 activity on human monocyte differentiation and function.   CD14+ peripheral blood monocytes were isolated from healthy volunteers and differentiated into macrophages using M-CSF, in the presence or absence of 10µM AMTB (TRPM8 antagonist).  RNA seq was performed on CD14+ monocytes and macrophages differentiated in vehicle(Mo-M-DMSO) or AMTB (Mo-M-AMTB).  To assess the transcriptional changes that normally occur in monocyte to macrophage differentiaiton we compared the Mo-M-DMSO and CD14+ monocyte samples. 3109 genes were significantly down-regulated and 3403 up-regulated in Mo-M-DMSO samples compared to CD14+ monocytes. To investigate the impact of AMTB upon macrophage differentiation we compared the Mo-M-DMSO and Mo-M-AMTB.  556 genes were significantly lower and 421 genes were significantly higher in Mo-M-AMTB samples compared to Mo-M-DMSO samples. 331 out of the 556  genes lower in Mo-M-AMTB samples were genes that were normally up-regulated during differentiaiton and  253 out of the 421 genes higher in the Mo-M-AMTB samples were genes that were normally down-regulated during differentiation indicating that AMTB predominantly acts to inhibit aspects of the differentiation programme. Overall design: Peripheral blood CD14+ monocytes from 5 healthy donors were differentiated into macrophages (Mo-M) by 6 days culture with M-CSF, in the presence of 10µM AMTB or vehicle (DMSO). PolyA+ RNA seq was performed on CD14+ monocytes, Mo-M-DMSO and Mo-M-AMTB samples.