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A local subset of mesenchymal cells expressing the transcription factor Osr1 orchestrates lymph node initiation

Item Type:Article
Title:A local subset of mesenchymal cells expressing the transcription factor Osr1 orchestrates lymph node initiation
Creators Name:Vallecillo-García, P. and Orgeur, M. and Comai, G. and Poehle-Kronnawitter, S. and Fischer, C. and Gloger, M. and Dumas, C.E. and Giesecke-Thiel, C. and Sauer, S. and Tajbakhsh, S. and Höpken, U.E. and Stricker, S.
Abstract:During development, lymph node (LN) initiation is coordinated by lymphoid tissue organizer (LTo) cells that attract lymphoid tissue inducer (LTi) cells at strategic positions within the embryo. The identity and function of LTo cells during the initial attraction of LTi cells remain poorly understood. Using lineage tracing, we demonstrated that a subset of Osr1-expressing cells was mesenchymal LTo progenitors. By investigating the heterogeneity of Osr1(+) cells, we uncovered distinct mesenchymal LTo signatures at diverse anatomical locations, identifying a common progenitor of mesenchymal LTos and LN-associated adipose tissue. Osr1 was essential for LN initiation, driving the commitment of mesenchymal LTo cells independent of neural retinoic acid, and for LN-associated lymphatic vasculature assembly. The combined action of chemokines CXCL13 and CCL21 was required for LN initiation. Our results redefine the role and identity of mesenchymal organizer cells and unify current views by proposing a model of cooperative cell function in LN initiation.
Keywords:Lymph Nodes, Initiation, Mesenchymal, Osr1, Retinoic Acid, Lymphatic Vessel, CXCL13
Source:Immunity
ISSN:1074-7613
Publisher:Cell Press / Elsevier
Volume:56
Number:6
Page Range:1204-1219
Date:13 June 2023
Official Publication:https://doi.org/10.1016/j.immuni.2023.04.014
PubMed:View item in PubMed

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