title: Single-Cell Gene Expression Analyses Reveal Heterogeneous Responsiveness of Fetal Innate Lymphoid Progenitors to Notch Signaling.
abstract: 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.
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France; University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75013 Paris, France; INSERM U1223, 75015 Paris, France.
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Chea
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France; Cytometry Platform, Institut Pasteur, 75015 Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Schmutz
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France; University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75013 Paris, France; INSERM U1223, 75015 Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Berthault
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France; University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75013 Paris, France; INSERM U1223, 75015 Paris, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Perchet
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France; University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75013 Paris, France; INSERM U1223, 75015 Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Petit
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France; University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75013 Paris, France; INSERM U1223, 75015 Paris, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Burlen-Defranoux
authors.affiliation: Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Ananda W
authors.initials: AW
authors.lastname: Goldrath
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, 69120 Heidelberg, Germany.
authors.forename: Hans-Reimer
authors.initials: HR
authors.lastname: Rodewald
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France; University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75013 Paris, France; INSERM U1223, 75015 Paris, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Cumano
authors.affiliation: Lymphopoiesis Unit, Immunology Department, Institut Pasteur, 75015 Paris, France; University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75013 Paris, France; INSERM U1223, 75015 Paris, France. Electronic address: rachel.golub@pasteur.fr.
authors.forename: Rachel
authors.initials: R
authors.lastname: Golub
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage / Q000276:immunology; D049109:Cell Proliferation; D005333:Fetus; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D007113:Immunity, Innate; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000276:immunology; D016023:Integrins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D051880:Receptors, Notch / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D059010:Single-Cell Analysis; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D014158:Transcription, Genetic; D059467:Transcriptome; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000276:immunology
chemical_list: C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D016023:Integrins; D051880:Receptors, Notch; C071777:integrin alpha4beta7; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3