In this issue of JEM , Hosokawa et al. ( https://doi.org/10.1084/jem.20190972 ) establish that transcription factor Bcl11b regulates almost completely distinct sets of genes in T cell precursors and ILC2s. To understand how this occurs, they identify multiple levels of functional regulation for Bcl11b that are used differently by T cell precursors and ILC2s.
Early innate lymphoid progenitors (EILPs) have recently been identified in mouse adult bone marrow as a multipotential progenitor population specified toward innate lymphoid cell (ILC) lineages, but their relationship with other described ILC progenitors is still unclear. In this study, we examine the progenitor–successor relationships between EILPs, all-lymphoid progenitors (ALPs), and ILC precursors (ILCps). Functional, bioinformatic, phenotypical, and genetic approaches collectively establish EILPs as an intermediate progenitor between ALPs and ILCps. Our work additionally provides new candidate regulators of ILC development and clearly defines the stage of requirement of transcription factors key for early ILC development.