Fig. 1.

Analysis pipeline. Primary macrophages from WKY and LEW are derived from the bone marrow after 3 day of culture and show a marked phenotypic difference in multinucleation and MGC formation, A. To understand the determinants of spontaneous macrophage multinucleation, we measure the macrophage transcriptome and phospho-proteome at day 3 (mononuclear and differentiated BMDMs) and in MGC precursors (day 5). MGC precursor-specific molecular signatures are next identified by determining transcriptional changes unique to WKY day 5 BMDMs B, and by characterizing multinucleation-specific transcription factors through transcription factor binding site enrichment analysis (C, step a). Finally, multinucleation-specific transcription factors and phosphopeptides are integrated by identifying pairs in closer than random vicinity in the protein interaction network (C, step b).