1. Polychromic Reporter Mice Reveal Unappreciated Innate Lymphoid Cell Progenitor Heterogeneity and Elusive ILC3 Progenitors in Bone Marrow
- Author
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Batika M. J. Rana, Jillian L. Barlow, Maria Daly, Sarah A. Teichmann, Noé Rodríguez-Rodríguez, James Cruickshank, Jennifer A. Walker, Richard Pannell, Paula A. Clark, Liora Haim-Vilmovsky, Helen E. Jolin, Alastair Crisp, Meera Sivasubramaniam, Ana Carolina Franco Ferreira, Aydan Szeto, and Andrew N. J. McKenzie
- Subjects
0301 basic medicine ,ILC development ,bone marrow ,Immunology ,Population ,Mice, Transgenic ,Biology ,Article ,Cell Line ,ILC progenitors ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Genes, Reporter ,Precursor cell ,medicine ,Immunology and Allergy ,Animals ,Cell Lineage ,Lymphocytes ,Progenitor cell ,education ,skin and connective tissue diseases ,Transcription factor ,Tissue homeostasis ,Progenitor ,Mice, Knockout ,education.field_of_study ,ILC3 progenitor ,Innate lymphoid cell ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Lymphoid Progenitor Cells ,Immunity, Innate ,Lymphocyte Subsets ,Cell biology ,body regions ,Killer Cells, Natural ,Mice, Inbred C57BL ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Bone marrow ,Single-Cell Analysis ,Transcription Factors - Abstract
Summary Innate lymphoid cells (ILCs) play strategic roles in tissue homeostasis and immunity. ILCs arise from lymphoid progenitors undergoing lineage restriction and the development of specialized ILC subsets. We generated “5x polychromILC” transcription factor reporter mice to delineate ILC precursor states by revealing the multifaceted expression of key ILC-associated transcription factors (Id2, Bcl11b, Gata3, RORγt, and RORα) during ILC development in the bone marrow. This approach allowed previously unattained enrichment of rare progenitor subsets and revealed hitherto unappreciated ILC precursor heterogeneity. In vivo and in vitro assays identified precursors with potential to generate all ILC subsets and natural killer (NK) cells, and also permitted discrimination of elusive ILC3 bone marrow antecedents. Single-cell gene expression analysis identified a discrete ILC2-committed population and delineated transition states between early progenitors and a highly heterogeneous ILC1, ILC3, and NK precursor cell cluster. This diversity might facilitate greater lineage potential upon progenitor recruitment to peripheral tissues., Highlights • Five-color “polychromILC” transcription factor reporter mice define ILC precursors • ILC precursors give rise to ILC1, ILC2, and ILC3 and retain NK potential • A RorcKat allele allows resolution of extremely rare ILC3 progenitors • Detection of divergent trajectories for ILC2 and common ILC1, ILC3, and NK development, Innate lymphoid cells (ILCs) play strategic roles in tissue homeostasis and immunity. Walker et al. demonstrate via five-reporter polychrome mice the distinct divergence of ILC2 development from common ILC1, ILC3, and NK progenitors.
- Published
- 2019