Journal
NATURE IMMUNOLOGY
Volume 20, Issue 9, Pages 1150-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-019-0445-7
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Funding
- Intramural Research Program of the NIH
- National Cancer Institute and Center for Cancer Research
- NIH [AI121080, AI139874]
- Veteran Affairs BLR&D Merit Review Program [BX002903A]
- Foundation pour la Recherche Medicale [DEQ20170839118]
- National Research Agency Investissements d'Avenir via the program LabEX IGO [ANR-11-LABX-0016-01]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZIAHL006030, ZIAHL006031] Funding Source: NIH RePORTER
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Innate lymphoid cells (ILCs) play important functions in immunity and tissue homeostasis, but their development is poorly understood. Through the use of single-cell approaches, we examined the transcriptional and functional heterogeneity of ILC progenitors, and studied the precursor-product relationships that link the subsets identified. This analysis identified two successive stages of ILC development within T cell factor 1-positive (TCF-1(+)) early innate lymphoid progenitors (EILPs), which we named 'specified EILPs' and 'committed EILPs'. Specified EILPs generated dendritic cells, whereas this potential was greatly decreased in committed EILPs. TCF-1 was dispensable for the generation of specified EILPs, but required for the generation of committed EILPs. TCF-1 used a pre-existing regulatory landscape established in upstream lymphoid precursors to bind chromatin in EILPs. Our results provide insight into the mechanisms by which TCF-1 promotes developmental progression of ILC precursors, while constraining their dendritic cell lineage potential and enforcing commitment to ILC fate.
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