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During embryogenesis, lymphoid tissue inducer (LTi) cells are essential for lymph node organogenesis. These cells are part of the innate lymphoid cell (ILC) family. Although their earliest embryonic hematopoietic origin is unclear, other innate immune cells have been shown to be derived from early hemogenic endothelium in the yolk sac as well as the aorta-gonad-mesonephros. A proper model to discriminate between these locations was unavailable. In this study, using a Cxcr4-CreERT2 lineage tracing model, we identify a major contribution from embryonic hemogenic endothelium, but not the yolk sac, toward LTi progenitors. Conversely, embryonic LTi cells are replaced by hematopoietic stem cell-derived cells in adults. We further show that, in the fetal liver, common lymphoid progenitors differentiate into highly dynamic alpha-lymphoid precursor cells that, at this embryonic stage, preferentially mature into LTi precursors and establish their functional LTi cell identity only after reaching the periphery. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.


Milesa Simic, Iris Manosalva, Lionel Spinelli, Rebecca Gentek, Raheleh R Shayan, Carole Siret, Mathilde Girard-Madoux, Shuaiwei Wang, Lauriane de Fabritus, Janneke Verschoor, Yann M Kerdiles, Marc Bajenoff, Ralf Stumm, Rachel Golub, Serge A van de Pavert. Distinct Waves from the Hemogenic Endothelium Give Rise to Layered Lymphoid Tissue Inducer Cell Ontogeny. Cell reports. 2020 Aug 11;32(6):108004

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PMID: 32783932

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