GSE163452
Effector differentiation downstream of lineage commitment in ILC1 is driven by Hobit across tissues.
Innate lymphoid cells (ILCs) mediate early immunity against infection and participate in tissue inflammation and homeostasis. It is unclear how ILCs acquire effector function, and whether these mechanisms differ between organs. Through multiplexed single-cell mRNA-sequencing we identified cKit+CD127hiTCF-1hi early differentiation stages of T-bet+ ILC1. These cells were present across different organs and had the potential to mature towards CD127intTCF-1int and CD127-TCF-1- ILC1. Paralleling a gradual loss of TCF-1, differentiating ILC1 forfeited their expansion potential while increasing expression of effector molecules, reminiscent of T cell differentiation in secondary lymphoid organs. The transcription factor Hobit was induced in TCF-1hi ILC1s and was required for their effector differentiation. These findings reveal sequential mechanisms of ILC1 lineage commitment and ILC1 effector differentiation that are conserved across tissues. Our analyses suggest that ILC1 emerge as TCF-1hi cells in the periphery and acquire a spectrum of organ-specific effector phenotypes through a uniform Hobit-dependent differentiation pathway driven by local cues. Overall design: Single cell mRNA sequencing of liver ILC1 and NK cells from WT and Hobit-deficient mice.