DIKUL - logo
E-viri
Recenzirano Odprti dostop
  • Deciphering the Innate Lymp...
    Seillet, Cyril; Mielke, Lisa A.; Amann-Zalcenstein, Daniela B.; Su, Shian; Gao, Jerry; Almeida, Francisca F.; Shi, Wei; Ritchie, Matthew E.; Naik, Shalin H.; Huntington, Nicholas D.; Carotta, Sebastian; Belz, Gabrielle T.

    Cell reports, 10/2016, Letnik: 17, Številka: 2
    Journal Article

    Innate lymphoid cells (ILCs) are enriched at mucosal surfaces, where they provide immune surveillance. All ILC subsets develop from a common progenitor that gives rise to pre-committed progenitors for each of the ILC lineages. Currently, the temporal control of gene expression that guides the emergence of these progenitors is poorly understood. We used global transcriptional mapping to analyze gene expression in different ILC progenitors. We identified PD-1 to be specifically expressed in PLZF+ ILCp and revealed that the timing and order of expression of the transcription factors NFIL3, ID2, and TCF-1 was critical. Importantly, induction of ILC lineage commitment required only transient expression of NFIL3 prior to ID2 and TCF-1 expression. These findings highlight the importance of the temporal program that permits commitment of progenitors to the ILC lineage, and they expand our understanding of the core transcriptional program by identifying potential regulators of ILC development. Display omitted •ILCp transcriptomics define the blueprint for hierarchical ILC development•PD-1 identifies the PLZF-expressing ILC precursor in the bone marrow•Transient NFIL3 expression prior to ID2 expression is required for ILC development•ID2 and TCF-1 are required to extinguish stem cell and B and T cell gene programs Seillet et al. define the hierarchical blueprint for ILC development using global transcriptomic analyses of ILC progenitors. This revealed that PD-1 is a key marker of ILCp and uncovered a regulatory circuit governed by NFIL3 in regulating ID2 and TCF-1 essential for ILC differentiation.