title: Single-cell analysis defines the divergence between the innate lymphoid cell lineage and lymphoid tissue-inducer cell lineage.
abstract: The precise lineage relationship between innate lymphoid cells (ILCs) and lymphoid tissue-inducer (LTi) cells is poorly understood. Using single-cell multiplex transcriptional analysis of 100 lymphoid genes and single-cell cultures of fetal liver precursor cells, we identified the common proximal precursor to these lineages and found that its bifurcation was marked by differential induction of the transcription factors PLZF and TCF1. Acquisition of individual effector programs specific to the ILC subsets ILC1, ILC2 and ILC3 was initiated later, at the common ILC precursor stage, by transient expression of mixed ILC1, ILC2 and ILC3 transcriptional patterns, whereas, in contrast, the development of LTi cells did not go through multilineage priming. Our findings provide insight into the divergent mechanisms of the differentiation of the ILC lineage and LTi cell lineage and establish a high-resolution 'blueprint' of their development.
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, Illinois, USA.|Department of Pathology, University of Chicago, Chicago, Illinois, USA.
authors.forename: Isabel E
authors.initials: IE
authors.lastname: Ishizuka
authors.affiliation: Institut Pasteur, Immunology Department, Lymphopoiesis Unit, Inserm U668, University Paris Diderot, Paris, France.
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Chea
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, Illinois, USA.|Institute of Biophysical Dynamics, University of Chicago, Chicago, Illinois, USA.|Department of Chemistry, University of Chicago, Chicago, Illinois, USA.
authors.forename: Herman
authors.initials: H
authors.lastname: Gudjonson
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, Illinois, USA.|Department of Pathology, University of Chicago, Chicago, Illinois, USA.
authors.forename: Michael G
authors.identifier: http://orcid.org/0000-0003-4770-7751
authors.initials: MG
authors.lastname: Constantinides
authors.affiliation: Institute of Biophysical Dynamics, University of Chicago, Chicago, Illinois, USA.|Department of Chemistry, University of Chicago, Chicago, Illinois, USA.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Dinner
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, Illinois, USA.|Department of Pathology, University of Chicago, Chicago, Illinois, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Bendelac
authors.affiliation: Institut Pasteur, Immunology Department, Lymphopoiesis Unit, Inserm U668, University Paris Diderot, Paris, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Golub
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000276:immunology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000276:immunology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice; D060885:Multiplex Polymerase Chain Reaction; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059010:Single-Cell Analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C513267:Zbtb16 protein, mouse