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

• DOI: 10.1038/ni.3248
• Publication Date: 2015-08-17T16:15:50Z
• Authors: Qi Yang; Fengyin Li; Christelle Harly; Shaojun Xing; Longyun Ye; Xuefeng Xia; Haikun Wang; Xinxin Wang; Shuyang Yu; Xinyuan Zhou; Maggie Cam; Hai-Hui Xue; Avinash Bhandoola
• Keywords: [SDV] Life Sciences [q-bio]; Mice; [SDV]Life Sciences [q-bio]; T Cell Transcription Factor 1; Animals; Bone Marrow Cells; Lymphocytes; Flow Cytometry; Microarray Analysis; Article; Cells, Cultured; Immunity, Innate; Up-Regulation

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.