Fig 1: Potential upstream regulators of genes differentially expressed between consecutive time points (DEGcts) in SF and ISF cultures. (A) Time window specific identification of upstream regulators analysis of the DEGcts using Ingenuity Pathway Analysis (IPA). The colored circles are upstream regulators identified for each comparison of consecutive time points with an activation or inhibition Z-score (> 2.0 or < -2.0), respectively (Supplementary Table 5). Colors of the circles correspond to colors of the module eigengene from WGCNA to which that specific gene associated. Activated upstream regulators are shown at the top and those inhibited at the bottom. Upstream regulators were grouped into five categories: `Transcription regulator’, `Membrane receptor’, `Cytokine/Growth Factor (GF)’, ‘Enzyme/Kinase’ and `Other’. (B) Interaction network among activated (left) and inhibited (right) upstream regulators in BMNC cultured in ISF. Color coding of nodes relate to the corresponding module eigengene. Interaction networks reflect a response to inflammation-induced oxidative stress associated with proliferation and differentiation of BMNC into macrophages (CSF1 - green arrow), and a PPAR?-reliant inflammation resolution (red arrow), associated with inhibition of the IL-1ß signaling pathway (black arrow) as suggested by complimentary analyses.