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Nat Immunol. 2015 Oct;16(10):1044-50. doi: 10.1038/ni.3248. Epub 2015 Aug 17.

TCF-1 upregulation identifies early innate lymphoid progenitors in the bone marrow.

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T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
CCR Collaborative Bioinformatics Resource, National Cancer Institute, Bethesda, Maryland, USA.


The cellular and molecular events that drive the early development of innate lymphoid cells (ILCs) remain poorly understood. We show that the transcription factor TCF-1 is required for the efficient generation of all known adult ILC subsets and their precursors. Using novel reporter mice, we identified a new subset of early ILC progenitors (EILPs) expressing high amounts of TCF-1. EILPs lacked efficient T and B lymphocyte potential but efficiently gave rise to NK cells and all known adult helper ILC lineages, indicating that they are the earliest ILC-committed progenitors identified so far. Our results suggest that upregulation of TCF-1 expression denotes the earliest stage of ILC fate specification. The discovery of EILPs provides a basis for deciphering additional signals that specify ILC fate.

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