Transcriptional control of macrophage diversity and specialization

The key driving force underlying cell identity is represented by the complex and dynamic interplay between cell-intrinsic, lineage-restricted developmental pathways on the one hand, and cell-extrinsic, tissue-specific microenvironmental signals on the other. In this context, macrophages are a paradigmatic cell population whose functional specialization in vivo reflects the impact of the local microenvironment on the intrinsic differentiation program, leading to a variety of specialized macrophage types in different tissues and conditions; however, how this is translated into a biological outcome is not appreciably understood. The kind of investigations described in this Viewpoint aim to explore the inner determinants of cell identity and functional diversification at a genomic level; mechanisms that permit plastic cell types, like macrophages, to adapt to different environments.