SIGNAL INTEGRATION AND TRANSCRIPTIONAL REGULATION OF THE INFLAMMATORY PROGRAM ASSOCIATED WITH THE GM-/M-CSF SIGNALING AXIS IN HUMAN MONOCYTES [METHYLATION DATA SET]

In recent years, the M-CSF and GM-CSF cytokines have been identified as opposing regulators of the inflammatory program. However, the two cytokines are simultaneously present in the inflammatory milieu, and it is not clear how cells integrate these signals. In order to understand the regulatory networks associated with the GM/M-CSF signaling axis we analyzed DNA methylation in human monocytes. Our results indicate that GM-CSF induces activation of the inflammatory program and extensive DNA methylation changes, while M-CSF-polarized cells are in a less differentiated state. This inflammatory program is mediated via JAK2 associated with the GM-CSF receptor and the downstream ERK signaling. However, PI3K signaling is associated with a negative regulatory loop of the inflammatory program and M-CSF autocrine signaling in GM-CSF-polarized monocytes. Our findings describe the regulatory networks associated with the GM/M-CSF signaling axis and how they contribute to the establishment of the inflammatory program associated with monocyte activation. Two replicates were used per cell type. Each sample of Monocytes, M1 and M2 were obtained from a pool of three individuals. Hematopoietic progenitors CD34+ were used as reference samples.