Plasticity in the transcriptional and epigenetic circuits regulating dendritic cell lineage specification and function

Dendritic cells (DC) are critical and functionally versatile innate immune sentinels. Here, we coarsely partition the adult DC lineage into three developmental subtypes and argue that pioneer transcription factors and chromatin remodeling are responsible for specification and plasticity between the DC subsets. Subsequently, intricate signaling-dependent transcription factor networks generate different functional states in response to pathogen stimuli within a specified DC subtype. To expand our understanding of lineage heterogeneity and functional activation states, we discuss the use of single cell genomics approaches in the context of a newly emerging systems immunology era, complementing the dichotomous definition of immune cells based solely on their surface marker expression. Rapid developments in single cell genomics are beginning to provide us with robust tools to potentially revise the working models of DC specification and the common hematopoietic tree.