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Single-Cell Gene Expression Analyses Reveal Heterogeneous Responsiveness of Fetal Innate Lymphoid Progenitors to Notch Signaling.

By Sylvestre Chea, Sandrine Schmutz, Claire Berthault, Thibaut Perchet, Maxime Petit, Odile Burlen-Defranoux, Ananda W Goldrath, Hans-Reimer Rodewald, Ana Cumano and Rachel Golub

Abstract

International audienceT and innate lymphoid cells (ILCs) share some aspects of their developmental programs. However, although Notch signaling is strictly required for T cell development, it is dispensable for fetal ILC development. Constitutive activation of Notch signaling, at the common lymphoid progenitor stage, drives T cell development and abrogates ILC development by preventing Id2 expression. By combining single-cell transcriptomics and clonal culture strategies, we characterize two heterogeneous α4β7-expressing lymphoid progenitor compartments. αLP1 (Flt3(+)) still retains T cell potential and comprises the global ILC progenitor, while αLP2 (Flt3(-)) consists of ILC precursors that are primed toward the different ILC lineages. Only a subset of αLP2 precursors is sensitive to Notch signaling required for their proliferation. Our study identifies, in a refined manner, the diversity of transitional stages of ILC development, their transcriptional signatures, and their differential dependence on Notch signaling

Topics: Notch signaling, T cell, Global ILC progenitor, [ SDV.IMM ] Life Sciences [q-bio]/Immunology
Publisher: Elsevier Inc
Year: 2016
DOI identifier: 10.1016/j.celrep.2016.01.015
OAI identifier: oai:HAL:pasteur-01289263v1
Provided by: Hal-Diderot

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