Dynamic Regulation of Innate Lymphoid Cell Development During Ontogeny

Dynamic composition of innate lymphoid cell (ILC) subsets in the small intestine during mouse ontogeny have been reported for more than ten years, but the underlying mechanisms remain incompletely understood. Here, we further confirmed a higher proportion of LTi cells in multiple tissues of fetal and new born mice, which decreased gradually with an increased proportion of non-LTi ILCs at the adult stage. Moreover, ILC progenitors showed a preferential differentiation towards LTi cells at the fetal stage, while at the adult stage, ILC progenitors differentiated mainly into non-LTi ILCs, consistent with the dynamic ILC subset composition from fetal to adult stages. However, through scRNA-seq analysis, we predicted a conserved trajectory of ILC development in the fetal liver and adult bone marrow, but the enhanced regulatory activity of Notch signaling and increased GATA3 expression in the adult-stage ILC progenitors, which suppressed ROR𝛾t expression, accounted for the transition from preferential LTi cell differentiation at the fetal stage to predominant non-LTi ILC differentiation at the adult stage. Accordingly, we propose a mechanism not described previously for the dynamic differentiation of ILC subsets, which may contribute to the dynamic change of ILC subset composition during ontogeny. ### Competing Interest Statement The authors have declared no competing interest.