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

Sylvestre Chea (1, 2) , Sandrine Schmutz (3, 1) , Claire Berthault (2, 1) , Thibaut Perchet (2, 1) , Maxime Petit (2, 1) , Odile Burlen-Defranoux (2, 1) , Ananda W Goldrath (4) , Hans-Reimer Rodewald (5) , Ana Cumano (2, 1) , Rachel Golub (2, 1)

1 Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4) - Lymphopoïèse
2 Cellule Pasteur
3 Cytométrie (Plate-forme)
4 Section of Molecular Biology, Division of Biological Sciences
5 division of cellular immunology

T 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.

Mots clés: Notch signaling; T cell; Global ILC progenitor

Domaines: Immunologie

Sylvestre Chea, Sandrine Schmutz, Claire Berthault, Thibaut Perchet, Maxime Petit, et al.. Single-Cell Gene Expression Analyses Reveal Heterogeneous Responsiveness of Fetal Innate Lymphoid Progenitors to Notch Signaling.. Cell Reports, 2016, The Cell Press Collection, 14 (6), pp.1500-16. ⟨10.1016/j.celrep.2016.01.015⟩. ⟨pasteur-01289263⟩